Generation of potent dominant negative transcriptional inhibitors

ABSTRACT

The present invention provides methods and compositions for regulating gene expression using transcription factors linked to proteins that localize to the transcriptional machinery.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit of U.S. Ser. No. 60/817,927,filed Jun. 30, 2006, herein incorporated by reference in its entirety.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH OR DEVELOPMENT

This invention was made with government support under Grant Nos. R01AI29135 and R41 CA103407, awarded by the National Institutes of Health.The government has certain rights in this invention.

BACKGROUND OF THE INVENTION

The regulation of gene expression by transcription factors is afundamental aspect of the physiology of all cells, whether prokaryoticor eukaryotic. In eukaryotic organisms, for instance, a variety oftranscription factors govern cell growth, differentiation, and death.The appropriate spatial and temporal expression of specifictranscription factors governs development. As examples, transcriptionfactors such as Myc and E2F control progression through the cell cycle;homeodomain, paired box, and forkhead transcription factors, amongothers, are involved in embryonic development; p53 is involved withtumor suppression and cell death; steroid hormone receptors, such as sexhormone, glucocorticoid, mineralocorticoid, and thyroid hormonereceptors have pleiotrophic effects on various aspects of physiology.

The aberrant expression of transcription factors can lead to abnormaldevelopment and various disease states. The inappropriate expression ofproto-oncogenes such as c-Myc through chromosomal translocation can leadto cancers such as Burkitt's lymphoma. The formation of a PML-RARafusion protein has been shown to be responsible for acute promyelocyticleukemia. Loss of p53 expression results in increased susceptibility tovarious cancers. The inappropriate expression or loss of expression ofheart specific transcription factors such as Tbx1, Tbx5, Nkx2.5, Gata4,Sal4, and Eya4 have been shown to result in congenital heart defects.

Improved methods for regulating gene expression by modulatingtranscription factor function would result in more optimal treatment ofmany diseases.

One disease which might be approached by modulating transcription factorfunction is acquired immune deficiency syndrome (AIDS). Humanimmunodeficiency virus (HIV) has been identified as the etiologicalagent responsible for AIDS, a fatal disease characterized by destructionof the immune system and the inability to fight off life threateningopportunistic infections. Recent statistics indicate that as many as 33million people worldwide are infected with the virus. In addition to thelarge number of individuals already infected, the virus continues tospread. Estimates from 1998 point to close to 6 million new infectionsin that year alone. In the same year there were approximately 2.5million deaths associated with HIV and AIDS.

HIV is a member of the class of viruses known as retroviruses. Theretroviral genome is composed of RNA, which is converted to DNA byreverse transcription. This retroviral DNA is then stably integratedinto a host cell's chromosome and, employing the replication machineryof the host cells, produces new retroviral particles and advances theinfection to other cells. HIV appears to have a particular affinity forthe human T-4 lymphocyte cell, which plays a vital role in the body'simmune system. HIV infection of these white blood cells depletes thiswhite cell population. Eventually, the immune system is renderedinoperative and ineffective against various opportunistic diseases suchas, among others, pneumocystic carini pneumonia, Kaposi's sarcoma, andcancer of the lymph system.

There are currently a number of antiviral drugs available to combat theinfection. These drugs can be divided into four classes based on theviral protein they target and their mode of action. In particular, oneclass of such antiviral drugs are competitive inhibitors of the aspartylprotease expressed by HIV. Other agents are nucleoside reversetranscriptase inhibitors that behave as substrate mimics to halt viralcDNA synthesis. A class of non-nucleoside reverse transcriptaseinhibitors inhibit the synthesis of viral cDNA via a non-competitive (oruncompetitive) mechanism. Another class are drugs that block viralfusion. Used alone, these drugs show effectiveness in reducing viralreplication. However, the effects are only temporary as the virusreadily develops resistance to all known agents.

As indicated above, a number of critical points in the HIV life cyclehave been identified as possible targets for antiviral drugs including(1) the initial attachment of the virion to the T-4 lymphocyte ormacrophage site; (2) the transcription of viral RNA to viral DNA(reverse transcriptase, RT); and (3) the processing of gag-pol proteinby HIV protease. An additional, potentially attractive therapeutictarget is transcription of the HIV genome. Transcription of the HIVgenome is essential for replication of the virus after integration ofviral DNA into a host cell chromosome. However, attempts to target HIVtranscription have been hampered, in part, by the fact thattranscription of the integrated HIV genome utilizes the host celltranscriptional machinery as well as viral transcription factors. Thus,therapies that attempt to target the transcription of the HIV genome mayalso interfere with transcription of normal host cell genes. Attemptshave been made to target specifically HIV transcription by thegeneration of dominant negative forms of Tat, a virally encodedtranscription factor. However, these dominant forms have been shown tohave poor activity at inhibiting HIV transcription and viralreplication.

Effective new methods to target underexploited aspects of the HIVlifecycle, such as transcription of the HIV genome would be desirable.

BRIEF SUMMARY OF THE INVENTION

The present application demonstrates that potent dominant negativeregulators of transcription can be generated by linking a transcriptionfactor to a protein that localizes to the transcriptional machinery.

In one embodiment, a method of regulating transcription of a gene isprovided in which a nucleic acid construct is expressed in a cell in anamount sufficient for modulation of transcription, where the constructcontains a first nucleic acid sequence encoding a transcription factorprotein or a fragment thereof linked to a second nucleic acid sequenceencoding a protein or a fragment thereof that localizes to thetranscriptional machinery. In various aspects, the transcription factorprotein can be viral transcription factors, nuclear proto-oncogene oroncogene proteins, nuclear tumor suppressor proteins, heart specifictranscription factors, and immune system transcription factors. In somefurther aspects, the viral transcription factors can be HIV-Tat, HPV-E2,HPV-E7, BPV-E2, Adenovirus IVa2, HSV-1 ICP4, EBNA-LP, EBNA-2, EBNA-3A,EBNA-3B, EBNA-3C, BZLF-1, CMV-IE-1, CMV-IE2, HHSV-8 K bZIP, HBV Hbx,Poxvirus Vaccinia, VETF, HCV NS5A, T-Ag, Adenovirus E1A, HerpesvirusVP16, HTLV Tax, Hepadnavirus X protein, or Baculovirus AcNPV IE-1. Insome further aspects, the nuclear proto-oncogene or oncogene proteinscan be Ab1, Myc, Myb, Re1, Jun, Fos, Sp1, Ap1, NF-κB, STAT 3 or 5,β-catenin, Notch, GLI, or PML-RARα. In some further aspects, heartspecific transcription factors can be Nkx 2, 3, 4, or 5, TBX5, GATA 4,5, or 6, or MEF2. In some further aspects, the immune cell specifictranscription factor can be Ikaros, PU.1, PAX-5, Oct-2, or BOB.1/OBF.1.

In various embodiments, the transcription factor can be a dominantnegative transcription factor, or fragment thereof. In furtherembodiments, the transcription factor can be either a transcriptionalactivator or repressor. In yet further embodiments, the transcriptionfactor can be an activation domain (AD) fragment of the transcriptionfactor. In yet further embodiments, the transcription factor can be Tator an activation domain fragment or other fragment of Tat.

In some embodiments, the protein or a fragment thereof that localizes tothe transcriptional machinery is a protein with nuclear localization, acomponent of the transcriptional machinery, or a protein that functionsin co-transcriptional processing of RNA. In some aspects, the proteinthat functions in co-transcriptional processing of RNA is a cappingfactor, a splicing factor, a polyadenylation factor, an RNA exportfactor, or a translation factor. In some aspects, the splicing factor isan RS domain containing protein. In yet other aspects, the splicingfactor is SF1, U2AF65, or 9G8, and the polyadenylation factor is CstF1.

In some embodiments, the modulation of transcription is inhibition oftranscription by at least 25%, or at least 50%, or at least 75%, or atleast 95%. In some aspects, the modulation of transcription is byinhibition of transcriptional initiation, or elongation, or termination.In some embodiments, the modulation of transcription is activation oftranscription.

In some embodiments, the cell is a T-cell infected with animmunodeficiency virus that can be HIV, FIV, SIV, or BIV. In yet furtherembodiments, the cell is a cancer cell, heart cell, or immune systemcell. In some aspects, the cancer cell is a carcinoma, sarcoma,adenocarcinoma, lymphoma, leukemia, or solid tumors of the kidney,breast, lung, bladder, colon, ovarian, prostate, pancreas, stomach,brain, head and neck, skin, uterine, testicular, glioma, esophagus, orliver. In some aspects, the immune system cell can be a B-cell, T-cell,macrophage, or dendritic cell.

Also included as embodiments are vectors and cells containing thenucleic acids of the embodiments above, as well as, the proteins encodedby these nucleic acids. In further aspects, a composition comprising thenucleic acid construct or protein of the above embodiments and aphysiologically acceptable carrier is provided.

In yet further embodiments, a method of regulating transcription of agene is provided by expressing a nucleic acid construct in a cell in anamount sufficient for modulation of transcription, in which theconstruct contains a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a splicing factor or a fragment thereof.

In still further embodiments, a method of inhibiting replication of animmunodeficiency virus by expressing a nucleic acid construct in a cellin an amount sufficient for modulation of viral transcription, in whichthe construct contains a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a protein or a fragment thereof thatlocalizes to the transcriptional machinery.

In another embodiment, provided is a method of inhibiting replication ofan immunodeficiency virus by expressing in a cell a nucleic acidconstruct in an amount sufficient for modulation of viral transcription,in which the construct contains a first nucleic acid sequence encoding aTat protein or a fragment thereof linked to a second nucleic acidsequence encoding a protein or a fragment thereof that localizes to thetranscriptional machinery.

In another embodiment, provided is a method of inhibiting replication ofan immunodeficiency virus by expressing in a cell a nucleic acidconstruct in an amount sufficient for modulation of viral transcription,in which the construct contains a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a splicing factor or a fragment thereof.

In another embodiment, provided is a method of treating a subjectinfected with an immunodeficiency virus by administering a nucleic acidconstruct in an amount sufficient for inhibition of viral transcription,in which the construct contains a first nucleic acid sequence encoding atranscription factor or a fragment thereof linked to a second nucleicacid sequence encoding a protein or a fragment thereof that localizes tothe transcriptional machinery. In some aspects, the treating is with aprotein of the embodiments above.

In another embodiment, provided is a method of inhibiting transcriptionof a HIV genome in a cell by expressing in the cell a nucleic acidconstruct in an amount sufficient for inhibition of the transcription ofthe HIV genome, in which the construct contains a first nucleic acidsequence encoding a Tat protein or a fragment thereof linked to a secondnucleic acid sequence encoding a U2AF65 protein or a fragment thereof.

In another embodiment, provided is a method of treating a subject withcancer by expressing in the subject a nucleic acid construct in anamount sufficient for modulation of transcription, in which theconstruct contains a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a protein or a fragment thereof thatlocalizes to the transcriptional machinery. In some aspects, thetreating is with a protein of the embodiments above.

In another embodiment, provided is a method of treating or preventing adisease in a subject by expressing in the subject a nucleic acidconstruct in an amount sufficient for modulation of transcription, inwhich the construct contains a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a protein or a fragment thereof thatlocalizes to the transcriptional machinery, where the disease is viralinfection, cancer, heart disease, and inflammation.

In another embodiment, provided is a method of validating a target byexpressing a nucleic acid construct in a cell in an amount sufficientfor modulation of transcription of the gene for the target, in which theconstruct contains a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a protein or a fragment thereof thatlocalizes to the transcriptional machinery, where altered expression ofthe gene for the target provides target confirmation.

DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a potent dominant negative Tat inhibitor identified in areporter assay. a, Left, Schematic of a dual reporter fluorescence assayin which T-BIV_(RBD) (HIV Tat_(AD) with the BIV Tat_(RBD)) is used toactivate an HIV LTR-DsRed reporter engineered with BIV TAR RNA in placeof HIV TAR. The T-SF1 fusion protein is used to activate an HIV LTR-GFPreporter engineered with a BPS RNA site. Right, HeLa cells wereco-transfected with both reporters and T-SF1 or T-BIV_(RBD) expressorsas indicated and sorted by flow cytometry. Expression of GFP is shown ingreen and DsRed in red. Numbers in each quadrant represent foldactivation, calculated as the number of cells in the quadrant multipliedby their average fluorescence, relative to the same values calculatedfor the reporters alone. b, Dose response curves of T-SF1 activation onan LTR-HTAR-FFL reporter and T-SF1-mediated inhibition of T-BIV_(RBD)activity on a LTR-BTAR-RL reporter. c, Potent inhibition by T-U2AF65 isindependent of the RNA-protein interaction. Left, dose response curvesshowing inhibition of T-BIV_(RBD)-mediated activation of a BIV TARreporter by Tat_(AD) and T-U2AF65. Right, dose response curves showinginhibition of T-Rev-mediated activation of a RREIIB reporter by Tat_(AD)and T-U2AF65. The arrows indicate stoichiometric DNA concentrations ofinhibitor and activator (5 ng). d, Promoter specificity of T-U2AF65.HeLa cells were transiently transfected with reporter, activator, andseveral concentrations of T-U2AF65 plasmids at the ratios indicated. Forthe heat shock response, endogenous HSF1 was activated 24 hrpost-transfection cells with 50 μM AsNO2 for 12 hr. p53 activity wasmeasured on SAOS2 cells. Activities of all activators were normalized toa cotransfected CMV-RL reporter control.

FIG. 2 shows contributions of subcellular localization and proteindomains to dominant negative activity. a, HeLa cells were transientlyco-transfected with an LTR-RREIIB-FFL reporter plasmid, T-Rev activator,and various inhibitors at 1:0.25 (grey bar) or 1:1 (black bar) ratios ofactivator to inhibitor. Activation levels are plotted relative to T-Revwithout inhibitor, and confocal images of each GFP-tagged inhibitor areshown below the plot, including 3× magnification images (of boxed cellsabove) to highlight the subcellular compartments. T-NLS contains the 8amino acid NLS of SV40 T-Ag (PPKKKRKV). b, Relative activities ofT-U2AF65 RS domain and Tat AD variants, as determined in panel a, withcorresponding confocal images. T-U2AF65ΔRS tagged with HA contains adeletion of the first 90 amino acids of U2AF65 and T-RS contains onlyresidues 2-73 of U2AF65. K41A denotes a Tat AD mutation that abolishesinteractions with cyclin T1 ₁₂. Confocal images of each HA-taggedinhibitor are shown below the plot, including 3× magnification images(of boxed cells above) to highlight the subcellular compartments.

FIG. 3 shows recruitment of the dominant negative to the HIV promotervia RNAP II blocks transcription elongation. a, T-U2AF65 interacts withRNAP II and P-TEFb. GFP-tagged T-U2AF65, T(K41A)-U2AF65 and T-NLSproteins were immunoprecipitated from cell extracts and analyzed byWestern blot using the indicated antibodies. b, T-U2AF65 colocalizeswith RNAP II and SC35 ₁₅. Following HeLa cell transfection, GFP-taggedT-U2AF65 was visualized by confocal microscopy along with immunostainedRNAP II and SC35. c, T-U2AF65 blocks transcription elongation. Cellswere transfected with Tat or T-U2AF65 as indicated, and RNase protectionwas performed with a promoter proximal (Pp) probe directed to the LTRand a promoter distal (Pd) probe directed to the FFL ORF to quantifytranscription rates in these regions of the LTR-HTAR-FFL reporter. d,Recruitment of RNAP II and T-U2AF65 to the HIV promoter. Left,activation and inhibition levels of a HeLa LTR-RREIIB-FFL reporter cellline used for CHIP assays, with the ratio of inhibitor to activationindicated. Right, CHIP assays from cells transfected with the HA- orGFP-tagged proteins indicated (panels 2-5) or untransfected cells (panel1), using antibodies directed against HA, GFP, or RNAP II and monitoringthe Pd and Pd regions. Mock lanes used normal rabbit IgG for the IP as aspecificity control, and input refers to PCR reactions from isolatedchromatin samples prior to the IP. e, Promoter-specific recruitment ofT-U2AF65. ChIP assays were carried out in HeLa LTR-RRE-IIB-FFL cellstransfected with T-U2AF65 or a T-NLS control using primers for HIV,gapdh, hsp70, p21/CIP, HLA-DRA and cad promoters. Known transcriptionfactors that activate each promoter are indicated in parentheses. Thepercent of input DNA is shown for each individual ChIP experiment, andthe amount of DNA used in the GFP lane is twice that for RNAP II.

FIG. 4 shows expression of the Tat dominant negative blocks HIVreplication and generates a latency-like state. Sup Ti cells stablyexpressing the Tat domains or fusion proteins indicated were infectedwith either HIV Tat-TAR-dependent (a) or BIV Tat-TAR-dependent (b)viruses (18) at an m.o.i. of 1 and the kinetics of p24 antigenexpression were monitored by ELISA. Viruses emerging from theinhibitor-expressing cell lines were harvested at day 30 (arrows) andused to re-infect the same cell lines from which they were derived, andidentical replication rates were observed.

FIG. 5. Tat RBD is dispensable for dominant negative activity. a, Doseresponse curves showing inhibition of BIV Tat-TAR-mediated activation byTat_(AD), Tat, T-U2AF65 and T-HIV_(RBD)AF65. The arrow indicates theposition of stoichiometric DNA concentrations (5 ng) of inhibitor andactivator. b, Dose response curves showing inhibition of HIVTat-TAR-mediated activation by Tat_(AD), T-BIV_(RBD), T-U2AF65 andT-BIV_(RBD)-U2AF65.

FIG. 6 shows relative expression levels of Tat activator and dominantnegative. HeLa cells were co-transfected with HA-tagged versions of theT-Rev activator and/or the T-U2AF65 inhibitor along with a GFP-expresorto normalize for transfection efficiency.

Nuclear extracts were probed for expression levels with an anti-HAantibody, an anti-GFP antibody, and an anti-C23 nucleolin antibody toprovide a protein loading control.

FIG. 7 shows inhibition activities of other T-fusions. HeLa cells wereco-transfected with an HIV LTR-RREIIB-FFL reporter plasmid along withthe T-Rev activator in the absence or presence of the N-terminalT-fusions at sub-stoichiometric 1:0.25 (black bars) or stoichiometric1:1 (gray bars) activator: inhibitor ratios. The data shown isnormalized to activation by T-Rev alone. Nuclear DAPI staining andindirect immunofluorescence confocal images of the activator and eachTat-fusion protein are shown above, using an anti-Tat antibody andAlexa-488 or Alexa-546 coupled anti-mouse antibodies.

FIG. 8 shows subnuclear localization of U2AF65, T-U2AF65, and variants.HeLa cells were transfected with pEGFP-N3 plasmids expressing GFP fusedto: U2AF65, T-U2AF65 (active dominant negative), T(K41A)-U2AF65(inactive dominant negative), RS (U2AF65 RS domain only), T-RS (activedominant negative), T(K41A)-RS (inactive dominant negative), U2AF65ΔRS,and T-U2ΔF65ΔRS.

FIG. 9 shows promoter-specificity of the dominant negative. a,Characterization of the SupT1 cell lines by luciferase reporter assays.The indicated SupT1 cell lines were co-transfected with an appropriateactivator and reporter pairs as shown. b, Total RNA was extracted fromSupT1-Tat_(AD) and SupT1-T-U2AF65 stable cell populations and relativemRNA levels of the nine genes shown were quantitated; β-actin (actin),glyceraldehyde-3-phosphate dehydrogenase (GAPDH), eukaryotic translationelongation factor 1 gamma (EEF1G), heterogeneous nuclearribonucleoprotein A1 (hnRNPA1), TATA box binding protein (TBP),hypoxanthine phosphoribosyltransferasel (HPRT1), HLA-DQA1 majorhistocompatibility complex, class II, (MHClI), Interleukin 8 (IL-8), andandrogen receptor (AR). Like HIV, the IL-8, androgen receptor, andHLA-DQA1 promoters require PTEF-b.

FIG. 10 shows re-infection of dominant negative-expressing cells withslowly-replicating viruses shows the same growth kinetics as the initialinfection. SupT1 cells expressing Tat_(AD) and T-U2AF65 were re-infectedwith viral stocks harvested from day 30 of the first set of infections(see arrows in FIGS. 4 a and 4 b). a, Re-infection using the HIVTat-TAR-dependent virus. b, Re-infection using the BIV Tat-TAR-dependentvirus.

DETAILED DESCRIPTION OF THE INVENTION

Introduction

The gene product of a dominant negative mutation interferes with thefunction of a normal, wild-type gene product within the same cell. Thisusually occurs if the gene product of the dominant negative mutation canstill interact with the same elements as the wild-type product, butblocks some aspect of the wild-type protein's function. As an example,in the case of multi-subunit protein complexes, an inactive dominantnegative protein can bind to wild-type components of the complexrendering the resulting complex less active or inactive. Geneticengineering has allowed the construction of dominant negative forms ofmany different types of proteins. In the case of transcription factors,one approach has been to generate transcription factors that lack a geneactivation domain but which retain a DNA binding domain. When expressedin cells, such dominant negative proteins are able to bind to theircognate DNA recognition sites thus preventing the binding of a wild typetranscription factor and leading to reduced expression of a target gene.However, typically, for dominant negative inhibition to occur, a greatexcess of dominant negative protein must be expressed in order toeffectively out compete the wild-type protein.

A dominant negative approach has previously been used in an attempt toinhibit transcription of the HIV genome and thus viral replication. Whena truncated form of Tat, lacking the basic domain, was tested intransient co-transfection experiments, it was found that an 8-30 foldmolar excess of the dominant negative Tat over wild-type Tat wasrequired to inhibit the expression of a reporter gene under the controlof the HIV-LTR.

The inventors have devised a new method of generating potent dominantnegative transcriptional inhibitors for pharmaceutical treatment ofdiseases, gene therapy, target validation, disease diagnosis, andmechanistic studies of transcription, among other applications. Asdiscussed above, previously described dominant negative transcriptionfactors typically act by competing with other interacting factors or bycreating defective oligomers, thus requiring a large excess of inhibitorwhile providing only a modest amount of inhibition. The inventors havediscovered that linking a protein which localizes to the transcriptionalmachinery to a transcription factor can effectively target and generatehigh local concentrations of a dominant negative protein, therebyefficiently out-competing wild-type protein when expressed atstoichiometric amounts. In particular, the inventors have made theunexpected finding that fusion of the Tat protein or a fragment thereof,such as the Tat activation domain (Tat AD), to a protein that localizesto the transcriptional machinery, results in a potent inhibitor oftranscription of the HIV genome. In particular, when Tat or Tat AD isfused to the splicing factors, SF1 or U2AF65, a potent dominant negativeeffect is observed. While one embodiment of this invention as describedbelow in the Examples relates to the inhibition of HIV transcription andviral replication, it will be clear to the skilled artisan that themethods of the present invention can be used to generate dominantnegative forms of other transcription factors and other classes ofproteins.

Dominant Negative Tat

Immediately after HIV infects a cell, the viral RNA is copied into DNA,and the proviral genome is transported to the nucleus where it isintegrated into the host genome. Once integrated into the hostchromosome, the HIV proviral genome is subject to regulation by avariety of cellular transcription factors, as well as, by virallyencoded factors. Among these virally encoded factors, thetrans-activator protein (Tat) provides the primary control of HIVtranscription.

Transcription of the HIV genome begins at the viral LTR when the hostcell RNA polymerase complex binds to the HIV promoter. The HIV LTR,however, is a poor promoter in the absence of Tat. In the absence ofTat, only non-processive (basal) transcription of the HIV genome isobserved. However, upon recruitment of Tat to the transcriptionalcomplex at the promoter, transcription of the HIV genome is greatlystimulated. Recruitment of Tat to the HIV promoter is mediated at leastin part by the binding of Tat to a short RNA sequence that forms astem-loop, termed the transactivation-responsive region (TAR), whichlies just downstream of the initiation site for transcription.Transcription of TAR by the basal transcriptional machinery to form theTAR RNA stem loop allows Tat to join the complex and stimulatetranscription. Upon binding of Tat, it is believed that other cellularfactors are recruited to the transcriptional complex that convert thecomplex into a form that is competent for processive transcriptelongation.

In one embodiment of this invention, the inventors have made a fusion ofthe Tat protein or a fragment thereof, such as the Tat activation domain(Tat AD), to proteins that localize to the transcriptional machinery.When Tat or Tat AD is fused to splicing factors, such as, SF1 or U2AF65,a potent dominant negative effect is observed. Without limitingthemselves to any particular mechanism of action, and as explained belowin greater detail, the inventors have found that the fused splicingfactor proteins act as tethering domains, directing the Tat fusionprotein to RNA polymerase at the HIV-1 promoter thus blocking theactivity of incoming wild-type Tat proteins. This results in a highlocal concentration of the inhibiting fusion protein at the site ofaction.

Definitions

As used herein, the following terms have the meanings ascribed to themunless specified otherwise.

A “dominant negative” gene product or protein is one that interfereswith the function of another gene product or protein. The other geneproduct affected can be the same or different from the dominant negativeprotein. Dominant negative gene products can be of many forms, includingtruncations, full length proteins with point mutations or fragmentsthereof, or fusions of full length wild type or mutant proteins orfragments thereof with other proteins. The level of inhibition observedcan be very low. For example, it may require a large excess of thedominant negative protein compared to the functional protein or proteinsinvolved in a process in order to see an effect. It may be difficult tosee effects under normal biological assay conditions.

A “transcription factor” is a protein that regulates transcription.Transcription factors may bind directly to DNA or RNA or may interactwith the transcriptional machinery via protein-protein interactions withno direct nucleic acid contact to modulate transcription. Transcriptionfactors in general are reviewed in Barnes and Adcock, Clin. Exp. Allergy25 Suppl. 2: 46-9 (1995), Roeder, Methods Enzymol. 273: 165-71 (1996),and Brivanlou and Darnell, Science 1 Feb. 2002: 813-818 (2002), amongother sources.

A “promoter” is defined as an array of nucleic acid control sequencesthat direct transcription. As used herein, a promoter typically includesnecessary nucleic acid sequences near the start site of transcription,such as, in the case of certain RNA polymerase II type promoters, a TATAelement, enhancer, CCAAT box, SP-1 site, etc. As used herein, a promoteralso optionally includes distal enhancer or repressor elements, whichcan be located as much as several thousand base pairs from the startsite of transcription. The promoters often have an element that isresponsive to transactivation by a DNA-binding moiety such as apolypeptide, e.g., a nuclear receptor, Gal4, the lac repressor and thelike.

A “target site” is the nucleic acid sequence recognized by atranscription factor protein. A single target site typically has aboutfour to about ten or more base pairs. The target site is in any positionthat allows regulation of gene expression, e.g., adjacent to, up- ordownstream of the transcription initiation site; proximal to an enhanceror other transcriptional regulation element such as a repressor (e.g.,SP-1 binding sites, hypoxia response elements, nuclear receptorrecognition elements, p53 binding sites, etc.), RNA polymerase pausesites; and intron/exon boundaries.

“Linking” or “fusing” as used in this application refers to entitiesthat are directly linked, or linked via an amino acid linker, the sizeand composition of which can vary, or linked via a chemical linker.

The term “transcriptional machinery” generally refers to the complex ofcellular components responsible for making RNA from a DNA template andrelated co-transcriptional RNA processing. The complex responsible fortranscription in a cell is referred to as RNA polymerase. Duringtranscription, a variety of factors join the RNA polymerase complex toeffect various aspects of transcription and co-transcriptional RNAprocessing as described below. In eukaryotic cells, three forms of RNApolymerase exist, termed RNA polymerases I, II, and III. RNA polymeraseI synthesizes a pre-rRNA 45S, which matures into 28 S, 18S and 5, 8 SrRNAs which form the major RNA portions of the ribosome. RNA polymeraseII synthesizes precursors of mRNAs and most snRNA. Because of the largevariety of cellular genes are transcribed by thus polymerase, RNAP II issubject to the highest level of control, requiring a wide range oftranscription factors depending on the promoter. RNA polymerase III isresponsible for the synthesis of tRNAs, rRNA 5S and other small RNAsfound in the nucleus and cytosol. Additionally, other RNA polymerasetypes are found in mitochondria and chloroplasts.

A 550 kDa complex of 12 subunits, RNAP II is the most intensivelystudied type of RNA polymerase. A wide range of transcription factorsare required for it to bind to its promoters and to begin transcription.In the process of transcription, there are three main stages: (1)initiation, which requires construction of the RNA polymerase complex onthe gene's promoter; (2) elongation, during which the RNA transcript ismade from the DNA template; (3) and termination, the step at which theformation of the RNA transcript is completed and disassembly of the RNApolymerase complex occurs.

The components of the transcriptional machinery that may be targeted bythis invention comprise any factor that is brought into the RNApolymerase complex and can be exemplified by the order in which the TAFs(TBP Associated Factors) attach to form a polymerase complex on apromoter. TBP (TATA Binding Protein) and an attached complex of TAFs,collectively known as TFIID (Transcription Factor for polymerase II D),bind at the TATA box, although not all promoters have the TATA box.TFIIA (three subunits) binds TFIID and DNA, stabilizing the firstinteractions. TFIIB binds between TFIID and the location of Pol IIbinding in the near future. TFIIB binds partially sequence specifically,with some preference for BRE. TFIIF and Pol II (two subunits, RAP30 andRAP74, showing some similarity to bacterial sigma factors) enter thecomplex together. TFIIF helps to speed up the polymerization process.TFIIE enters the complex, and helps to open and close the PolII's ‘Jaw’like structure, which enables movement down the DNA strand. TFIIE andTFIIH enter concomitantly. Finally TFIIH binds. TFIIH is a large proteincomplex that contains among others the CDK7/cyclin H kinase complex anda DNA helicase. TFIIH has three functions: it binds specifically to thetemplate strand to ensure that the correct strand of DNA is transcribedand melts or unwinds the DNA (ATP dependently) to separate the twostrands using its Helicase activity. It has a kinase activity thatphosphorylates the C-terminal domain (CTD) of Pol II at the amino acidserine. This switches the RNA polymerase to start producing RNA, whichmarks the end of initiation and the start of elongation. Finally it isessential for Nucleotide Excision Repair (NER) of damaged DNA. TFIIH andTFIIE strongly interact with one another. TFIIE affects TFIIH'scatalytic activity. Without TFIIE, TFIIH will not unwind the promoter.Mediator then encases all the transcription factors and the Pol II.Mediator interacts with enhancers, areas very far away (upstream ordownstream) that help regulate transcription.

A “protein that localizes to the transcriptional machinery” is one thatis capable of associating or interacting with the transcriptionalmachinery as described above or a component thereof. The association orinteraction may be non-covalent or covalent and may be reversible ornon-reversible. Examples of proteins that localize to thetranscriptional machinery include nuclear localized proteins, RNAprocessing proteins, components of the transcriptional machinery, andproteins involved in co-transcriptional processes. Among theco-transcriptional processes that are subjects of the invention arecapping, splicing, polyadenylation, RNA export, translation.

An RS domain containing protein (also referred to in the literature asan SR protein) is a protein with a domain that contains multiplearginine and serine di-peptides (single-letter code RS) and/or serineand arginine di-peptides (single-letter code SR). RS domains are foundin a number of cellular proteins, particularly those involved withpre-mRNA splicing and RNA processing events.

A “transcriptional activator” and a “transcriptional repressor” refer toproteins or effector domains of proteins that have the ability tomodulate transcription, by binding directly to DNA or RNA or byinteracting with the transcriptional machinery via protein-proteininteractions with no direct nucleic acid contact. Such proteins include,e.g., transcription factors and co-factors (e.g., KRAB, MAD, ERD, SID,nuclear factor kappa B subunit p65, early growth response factor 1, andnuclear hormone receptors, VP 16, VP64), endonucleases, integrases,recombinases, methyltransferases, histone acetyltransferases, histonedeacetylases etc. Activators and repressors include co-activators andco-repressors (see, e.g., Utley et al., Nature 394:498-502 (1998)).

The terms “modulating transcription” “inhibiting transcription” and“activating transcription” of a gene refer to the ability of a dominantnegative to activate or inhibit transcription of a gene. Activationincludes prevention of transcriptional inhibition (i.e., prevention ofrepression of gene expression) and inhibition includes prevention oftranscriptional activation (i.e., prevention of gene activation).

Modulation can be assayed by determining any parameter that isindirectly or directly affected by the expression of the target gene.Such parameters include, e.g., changes in RNA or protein levels, changesin protein activity, changes in product levels, changes in downstreamgene expression, changes in reporter gene transcription (luciferase,CAT, β-galactosidase, β-glucuronidase, GFP (see, e.g., Mistili &Spector, Nature Biotechnology 15:961-964 (1997)); changes in signaltransduction, phosphorylation and dephosphorylation, receptor-ligandinteractions, second messenger concentrations (e.g., cGMP, cAMP, IP3,and Ca²⁺), cell growth, and neovascularization. These assays can be invitro, in vivo, and ex vivo. Such functional effects can be measured byany means known to those skilled in the art, e.g., measurement of RNA orprotein levels, measurement of RNA stability, identification ofdownstream or reporter gene expression, e.g., via chemiluminescence,fluorescence, colorimetric reactions, antibody binding, induciblemarkers, ligand binding assays; changes in intracellular secondmessengers such as cGMP and inositol triphosphate (IP3); changes inintracellular calcium levels; cytokine release, and the like.

To determine the level of gene expression modulation by a dominantnegative construct, cells contacted with nucleic acids encoding dominantnegative or dominant negative proteins are compared to control cellswhich have not received this treatment. Control samples are assigned arelative gene expression activity value of 100%. Modulation/inhibitionof gene expression is achieved when the gene expression activity valuerelative to the control is about 80%, preferably 50% (i.e., 0.5x theactivity of the control), more preferably 25%, more preferably 5-0%.Modulation/activation of gene expression is achieved when the geneexpression activity value relative to the control is 110% , morepreferably 150% (i.e., 1.5x the activity of the control), morepreferably 200-500%, more preferably 1000-2000% or more.

The term “heterologous” is a relative term, which when used withreference to portions of a nucleic acid indicates that the nucleic acidcomprises two or more subsequences that are not found in the samerelationship to each other in nature. For instance, a nucleic acid thatis recombinantly produced typically has two or more sequences fromunrelated genes synthetically arranged to make a new functional nucleicacid, e.g., a promoter from one source and a coding region from anothersource. The two nucleic acids are thus heterologous to each other inthis context. When added to a cell, the recombinant nucleic acids wouldalso be heterologous to the endogenous genes of the cell. Thus, in achromosome, a heterologous nucleic acid would include an non-native(non-naturally occurring) nucleic acid that has integrated into thechromosome, or a non-native (non-naturally occurring) extrachromosomalnucleic acid. In contrast, a naturally translocated piece of chromosomewould not be considered heterologous in the context of this patentapplication, as it comprises an endogenous nucleic acid sequence that isnative to the mutated cell.

Similarly, a heterologous protein indicates that the protein comprisestwo or more subsequences that are not found in the same relationship toeach other in nature (e.g., a “fusion protein,” where the twosubsequences are encoded by a single nucleic acid sequence). See, e.g.,Ausubel, supra, for an introduction to recombinant techniques.

The term “recombinant” when used with reference, e.g., to a cell, ornucleic acid, protein, or vector, indicates that the cell, nucleic acid,protein or vector, has been modified by the introduction of aheterologous nucleic acid or protein or the alteration of a nativenucleic acid or protein, or that the cell is derived from a cell somodified. Thus, for example, recombinant cells express genes that arenot found within the native (naturally occurring) form of the cell orexpress a second copy of a native gene that is otherwise normally orabnormally expressed, under expressed or not expressed at all.

An “expression vector” is a nucleic acid construct, generatedrecombinantly or synthetically, with a series of specified nucleic acidelements that permit transcription of a particular nucleic acid in ahost cell, and optionally integration or replication of the expressionvector in a host cell. The expression vector can be part of a plasmid,virus, or nucleic acid fragment, of viral or non-viral origin.Typically, the expression vector includes an “expression cassette,”which comprises a nucleic acid to be transcribed operably linked to apromoter. The term expression vector also encompasses naked DNA operablylinked to a promoter.

By “host cell” is meant a cell that contains an expression vector ornucleic acid encoding a dominant negative protein of the invention. Thehost cell typically supports the replication or expression of theexpression vector. Host cells may be prokaryotic cells such as E. coli,or eukaryotic cells such as yeast, fungal, protozoal, higher plant,insect, or amphibian cells, or mammalian cells such as CHO, HeLa, 293,COS-1, and the like, e.g., cultured cells (in vitro), explants andprimary cultures (in vitro and ex vivo), and cells in vivo.

“Nucleic acid” refers to deoxyribonucleotides or ribonucleotides andpolymers thereof in either single- or double-stranded form. The termencompasses nucleic acids containing known nucleotide analogs ormodified backbone residues or linkages, which are synthetic, naturallyoccurring, and non-naturally occurring, which have similar bindingproperties as the reference nucleic acid, and which are metabolized in amanner similar to the reference nucleotides. Examples of such analogsinclude, without limitation, phosphorothioates, phosphoramidates, methylphosphonates, chiral-methyl phosphonates, 2-O-methyl ribonucleotides,peptide-nucleic acids (PNAs).

Unless otherwise indicated, a particular nucleic acid sequence alsoimplicitly encompasses conservatively modified variants thereof (e.g.,degenerate codon substitutions) and complementary sequences, as well asthe sequence explicitly indicated. Specifically, degenerate codonsubstitutions may be achieved by generating sequences in which the thirdposition of one or more selected (or all) codons is substituted withmixed-base and/or deoxyinosine residues (Batzer et al., Nucleic AcidRes. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608(1985); Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). The termnucleic acid is used interchangeably with gene, cDNA, mRNA,oligonucleotide, and polynucleotide.

The terms “polypeptide,” “peptide” and “protein” are usedinterchangeably herein to refer to a polymer of amino acid residues. Theterms also apply to amino acid polymers in which one or more amino acidresidues is an artificial chemical mimetic of a corresponding naturallyoccurring amino acid, as well as to naturally occurring amino acidpolymers and non-naturally occurring amino acid polymer.

The term “amino acid” refers to naturally occurring and synthetic aminoacids, as well as amino acid analogs and amino acid mimetics thatfunction in a manner similar to the naturally occurring amino acids.Naturally occurring amino acids are those encoded by the genetic code,as well as those amino acids that are later modified, e.g.,hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acidanalogs refers to compounds that have the same basic chemical structureas a naturally occurring amino acid, i.e., an α carbon that is bound toa hydrogen, a carboxyl group, an amino group, and an R group, e.g.,homoserine, norleucine, methionine sulfoxide, methionine methylsulfonium. Such analogs have modified R groups (e.g., norleucine) ormodified peptide backbones, but retain the same basic chemical structureas a naturally occurring amino acid. Amino acid mimetics refers tochemical compounds that have a structure that is different from thegeneral chemical structure of an amino acid, but that functions in amanner similar to a naturally occurring amino acid.

Amino acids may be referred to herein by either their commonly knownthree letter symbols or by the one-letter symbols recommended by theIUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise,may be referred to by their commonly accepted single-letter codes.

“Conservatively modified variants” applies to both amino acid andnucleic acid sequences. With respect to particular nucleic acidsequences, conservatively modified variants refers to those nucleicacids which encode identical or essentially identical amino acidsequences, or where the nucleic acid does not encode an amino acidsequence, to essentially identical sequences. Because of the degeneracyof the genetic code, a large number of functionally identical nucleicacids encode any given protein. For instance, the codons GCA, GCC, GCGand GCU all encode the amino acid alanine. Thus, at every position wherean alanine is specified by a codon, the codon can be altered to any ofthe corresponding codons described without altering the encodedpolypeptide. Such nucleic acid variations are “silent variations,” whichare one species of conservatively modified variations. Every nucleicacid sequence herein which encodes a polypeptide also describes everypossible silent variation of the nucleic acid. One of skill willrecognize that each codon in a nucleic acid (except AUG, which isordinarily the only codon for methionine, and TGG, which is ordinarilythe only codon for tryptophan) can be modified to yield a functionallyidentical molecule. Accordingly, each silent variation of a nucleic acidwhich encodes a polypeptide is implicit in each described sequence.

As to amino acid sequences, one of skill will recognize that individualsubstitutions, deletions or additions to a nucleic acid, peptide,polypeptide, or protein sequence which alters, adds or deletes a singleamino acid or a small percentage of amino acids in the encoded sequenceis a “conservatively modified variant” where the alteration results inthe substitution of an amino acid with a chemically similar amino acid.Conservative substitution tables providing functionally similar aminoacids are well known in the art. Such conservatively modified variantsare in addition to and do not exclude polymorphic variants, interspecieshomologs, and alleles of the invention.

The following eight groups each contain amino acids that areconservative substitutions for one another:

-   1) Alanine (A), Glycine (G);-   2) Aspartic acid (D), Glutamic acid (E);-   3) Asparagine (N), Glutamine (Q);-   4) Arginine (R), Lysine (K);-   5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V);-   6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W);-   7) Serine (S), Threonine (T); and-   8) Cysteine (C), Methionine (M)    (see, e.g., Creighton, Proteins (1984)).

The term “substantially identical” indicates that two or more nucleotidesequences share a majority of their sequence. Generally, this will be atleast about 90% of their sequence and preferably about 95% of theirsequence. Another indication that sequences are substantially identicalis if they hybridize to the same nucleotide sequence under stringentconditions (see, e.g., Sambrook and Russell, eds, Molecular Cloning: ALaboratory Manual, 3rd Ed, vols. 1-3, Cold Spring Harbor LaboratoryPress, 2001; and Current Protocols in Molecular Biology, Ausubel, ed.John Wiley & Sons, Inc. New York, 1997). Stringent conditions aresequence-dependent and will be different in different circumstances.Generally, stringent conditions are selected to be about 5° C. (or less)lower than the thermal melting point (Tm) for the specific sequence at adefined ionic strength and pH. The T_(m) of a DNA duplex is defined asthe temperature at which 50% of the nucleotides are paired andcorresponds to the midpoint of the spectroscopic hyperchromic absorbanceshift during DNA melting. The T_(m) indicates the transition from doublehelical to random coil.

Typically, stringent conditions will be those in which the saltconcentration is about 0.2×SSC at pH 7 and the temperature is at leastabout 60° C. For example, a nucleic acid of the invention or fragmentthereof can be identified in standard filter hybridizations using thenucleic acids disclosed here under stringent conditions, which forpurposes of this disclosure, include at least one wash (usually 2) in0.2×SSC at a temperature of at least about 60° C., usually about 65° C.,sometimes 70° C. for 20 minutes, or equivalent conditions. For PCR, anannealing temperature of about 5° C. below Tm, is typical for lowstringency amplification, although annealing temperatures may varybetween about 32° C. and 72° C., e.g., 40° C., 42° C., 45° C., 52° C.,55° C., 57° C., or 62° C., depending on primer length and nucleotidecomposition or high stringency PCR amplification, a temperature at, orslightly (up to 5° C.) above, primer Tm is typical, although highstringency annealing temperatures can range from about 50° C. to about72° C., and are often 72° C., depending on the primer and bufferconditions (Ahsen et al., Clin Chem. 47:1956-61, 2001). Typical cycleconditions for both high and low stringency amplifications include adenaturation phase of 90° C.-95° C. for 30 sec-2 min., an annealingphase lasting 30 sec.-10 min., and an extension phase of about 72° C.for 1-15 min.

The terms “identical” or percent “identity,” in the context of two ormore nucleic acids, refer to two or more sequences or subsequences thatare the same or have a specified percentage of nucleotides that are thesame (i.e., at least 70% identity, preferably at least 75%, 80%, 85%,90%, 95%, 96%, 97%, 98%, or 99% identity, over a specified region, whencompared and aligned for maximum correspondence over a comparisonwindow, or designated region as measured using a BLAST or BLAST 2.0sequence comparison algorithms with default parameters described below,or by manual alignment and visual inspection. Such sequences are thensaid to be “substantially identical.” This definition also refers to thecomplement of a test sequence. Preferably, the identity exists over aregion that is at least about 15, 20 or 25 nucleotides in length, ormore preferably over a region that is 50-100 nucleotides in length.

For sequence comparison, typically one sequence acts as a referencesequence, to which test sequences are compared. When using a sequencecomparison algorithm, test and reference sequences are entered into acomputer, subsequence coordinates are designated, if necessary, andsequence algorithm program parameters are designated. Default programparameters can be used, or alternative parameters can be designated. Thesequence comparison algorithm then calculates the percent sequenceidentities for the test sequences relative to the reference sequence,based on the program parameters.

A “comparison window”, as used herein, includes reference to a segmentof any one of the number of contiguous positions selected from the groupconsisting of from 15 to 600, usually about 20 to about 200, moreusually about 50 to about 150 in which a sequence may be compared to areference sequence of the same number of contiguous positions after thetwo sequences are optimally aligned. Methods of alignment of sequencesfor comparison are well-known in the art. Optimal alignment of sequencesfor comparison can be conducted, e.g., by the local homology algorithmof Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homologyalignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970),by the search for similarity method of Pearson & Lipman, Proc. Nat'l.Acad. Sci. USA 85:2444 (1988), by computerized implementations of thesealgorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin GeneticsSoftware Package, Genetics Computer Group, 575 Science Dr., Madison,Wis.), or by manual alignment and visual inspection (see, e.g., CurrentProtocols in Molecular Biology (Ausubel et al., eds. 1995 supplement)).

A preferred example of algorithm that is suitable for determiningpercent sequence identity and sequence similarity are the BLAST andBLAST 2.0 algorithms, which are described in Altschul et al., Nuc. AcidsRes. 25:3389-3402 (1977) and Altschul et al., J. Mol. Biol. 215:403-410(1990), respectively. BLAST and BLAST 2.0 are used, with the defaultparameters described herein, to determine percent sequence identity forthe nucleic acids described herein. Software for performing BLASTanalyses is publicly available through the National Center forBiotechnology Information. This algorithm involves first identifyinghigh scoring sequence pairs (HSPs) by identifying short words of lengthW in the query sequence, which either match or satisfy somepositive-valued threshold score T when aligned with a word of the samelength in a database sequence. T is referred to as the neighborhood wordscore threshold (Altschul et al., supra). These initial neighborhoodword hits act as seeds for initiating searches to find longer HSPscontaining them. The word hits are extended in both directions alongeach sequence for as far as the cumulative alignment score can beincreased. Cumulative scores are calculated using, for nucleotidesequences, the parameters M (reward score for a pair of matchingresidues; always>0) and N (penalty score for mismatching residues;always<0). Extension of the word hits in each direction are halted when:the cumulative alignment score falls off by the quantity X from itsmaximum achieved value; the cumulative score goes to zero or below, dueto the accumulation of one or more negative-scoring residue alignments;or the end of either sequence is reached. The BLAST algorithm parametersW, T, and X determine the sensitivity and speed of the alignment. TheBLASTN program (for nucleotide sequences) uses as defaults a word length(W) of 11, an expectation (E) of 10, M=5, N=−4 and a comparison of bothstrands.

The BLAST algorithm also performs a statistical analysis of thesimilarity between two sequences (see, e.g., Karlin & Altschul, Proc.Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarityprovided by the BLAST algorithm is the smallest sum probability (P(N)),which provides an indication of the probability by which a match betweentwo nucleotide sequences would occur by chance. For example, a nucleicacid is considered similar to a reference sequence if the smallest sumprobability in a comparison of the test nucleic acid to the referencenucleic acid is less than about 0.2, more preferably less than about0.01, and most preferably less than about 0.001.

“Administering” an expression vector, nucleic acid, protein, or adelivery vehicle to a cell comprises transducing, transfecting,electroporating, translocating, fusing, phagocytosing, shooting orballistic methods, etc., i.e., any means by which a protein or nucleicacid can be transported across a cell membrane and preferably into thenucleus of a cell.

A “delivery vehicle” refers to a compound, e.g., a liposome, toxin, or amembrane translocation polypeptide, which is used to administer dominantnegative proteins. Delivery vehicles can also be used to administernucleic acids encoding dominant negative proteins of the invention,e.g., a lipid:nucleic acid complex, an expression vector, a virus, andthe like.

Design of Dominant Negative Proteins

The dominant negative proteins of the invention comprise any of a numberof possible fusions of a transcription factor or other protein, orfragment thereof, with a protein that is capable of localization to thetranscriptional machinery, such as nuclear localized proteins, RNAprocessing proteins, components of the transcriptional machinery, andproteins involved in co-transcriptional processes. Among theco-transcriptional processes that are subjects of the invention arecapping, splicing, polyadenylation, RNA export, translation. Thetranscription factor can be derived from any of a number of speciesincluding, and not limited to, viruses, HIV, bacteria, yeast,Drosophila, C. elegans, Xenopus, mouse, monkey, and human. For humanapplications, a human TF is generally preferred. One of skill in the artwill recognize that a wide variety of transcription factor proteinsknown in the art may be used in this invention. See Goodrich et al.,Cell 84:825-30 (1996), Barnes & Adcock, Clin. Exp. Allergy 25 Suppl.2:46-9 (1995), and Roeder, Methods Enzymol. 273:165-71 (1996) forgeneral reviews of transcription factors. Databases dedicated totranscription factors are known (see, e.g., Science 269:630 (1995)).Nuclear hormone receptor transcription factors are described in, forexample, Rosen et al., J. Med. Chem. 38:4855-74 (1995). The C/EBP familyof transcription factors are reviewed in Wedel et al., Immunobiology193:171-85 (1995). Coactivators and co-repressors that mediatetranscription regulation by nuclear hormone receptors are reviewed in,for example, Meier, Eur. J. Endocrinol. 134(2):158-9 (1996); Kaiser etal., Trends Biochem. Sci. 21:342-5 (1996); and Utley et al., Nature394:498-502 (1998)). GATA transcription factors, which are involved inregulation of hematopoiesis, are described in, for example, Simon, Nat.Genet. 11:9-11 (1995); Weiss et al., Exp. Hematol. 23:99-107. TATA boxbinding protein (TBP) and its associated TAF polypeptides (which includeTAF30, TAF55, TAF80, TAF110, TAF150, and TAF250) are described inGoodrich & Tjian, Curr. Opin. Cell Biol. 6:403-9 (1994) and Hurley,Curr. Opin. Struct. Biol. 6:69-75 (1996). The STAT family oftranscription factors are reviewed in, for example, Barahmand-Pour etal., Curr. Top. Microbiol. Immunol. 211:121-8 (1996). Transcriptionfactors involved in disease are reviewed in Aso et al., J. Clin. Invest.97:1561-9 (1996).

As further examples, the transcription factor may be chosen from any ofa number of different classes of known transcription factors such asthose that contain homeodomains, POU domains, Helix-Loop-Helix (HLH),Zinc Fingers, Leucine Zippers, or Winged Helix, to name but a few of thestructural motifs found in transcription factors. Currently, there areabout 2000 known transcription factors. See, e.g., Brivanlou andDarnell, Science, 295: 813-818 (2002). Among some of the better knowntranscription factors include: c-Myc and Max, c-Fos and c-Jun, CREB,c-ErbA, c-Ets, GATA c-Myb, MyoD KF-kB, RAR, and SRF, to name a few.

Among the classes of transcription factors that find use in thisinvention are viral transcription factors, nuclear proto-oncogene oroncogene proteins, nuclear tumor suppressor proteins, heart specifictranscription factors, and immune cell transcription factors. The viraltranscription factors useful in the practice of this invention include:HIV-Tat, HPV-E2, HPV-E7, BPV-E2, Adenovirus IVa2, HSV-1 ICP4, EBNA-LP,EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C, BZLF-1, CMV-IE-1, CMV-IE2, HHSV-8 KbZIP, HBV Hbx, Poxvirus Vaccinia, VETF, HCV NS5A, T-Ag, Adenovirus E1A,Herpesvirus VP16, HTLV Tax, Hepadnavirus X protein, and BaculovirusAcNPV IE-1, among others. The nuclear proto-oncogene or oncogeneproteins and nuclear tumor suppressor proteins transcription factorsuseful in the practice of this invention include: Ab1, Myc, Myb, Re1,Jun, Fos, Sp1, Ap1, NF-κB, STAT 3 or 5, β-catenin, Notch, GLI, PML-RARαand p53, among others. The heart specific transcription factors usefulin the practice of this invention include: Nkx 2, 3, 4, or 5, TBX5, GATA4, 5, or 6, and MEF2, among others. The immune cell specifictranscription factors useful in the practice of this invention include:Ikaros, PU.1, PAX-5, Oct-2, and BOB.1/OBF.1, among others. A nonlimiting list of transcription factors that may be used in the practiceof this invention is provided in Table 3. The transcription factorsuseful in the practice of this invention can be human as well as derivedfrom yeast or higher eukaryotes such as viruses, HIV, Drosophila, C.elegans, Xenopus, or mouse, among other species.

In the practice of this invention, the transcription factor can beeither a transcriptional activator or repressor, examples of which arewell known in the art. Non-limiting examples of transcriptionalactivators and repressors are provided in Table 3.

Proteins that localize to the transcriptional machinery include:components of the transcriptional machinery, nuclear localized proteins,RNA processing proteins, components of the transcriptional machinery,and proteins involved in co-transcriptional processes and RNAprocessing.

Among the components of the transcriptional machinery that may be usedin the practice of this invention are TAFs, CDK7, cyclin H, DNAhelicase, unwinding enzymes, transcription factors, among others.

A wide range of proteins have been shown to localize to the nucleus andmay be used in the practice of this invention. A non-limiting list ofsuch proteins is provided in Table 1.

Among the co-transcriptional processes and RNA processing activitiesthat are subjects of the invention are capping, splicing,polyadenylation, RNA export, and translation. Accordingly, proteinsinvolved in capping, splicing, polyadenylation, RNA export, andtranslation may be used in the practice of this invention. Splicingfactors represent one particular class of proteins involved inco-transcriptional processing of RNA and are suitable for the practiceof this invention. As many as 300 factors are known to comprise thespliceosome. The protein components of spliceosomes are disclosed inRappsilber, J., Ryder, U., Lamond, A. I., and Mann, M. (2002) Genome Res12(8), 1231-1245 and Zhou, Z., Licklider, L. J., Gygi, S. P., and Reed,R. (2002) Nature 419(6903), 182-185, among other sources. Many splicingfactors useful for the practice of this invention are compiled in Table2. Particular examples of splicing factors useful in the practice ofthis invention include SF1, U2AF65, and 9G8.

The RS domain is a structural and functional feature characteristic ofmany nuclear proteins, particularly splicing factors. A large number ofRS domain proteins are known in the art, and many have been identifiedthrough a genome-wide survey of RS domain proteins from various species.See Boucher et al., RNA 7:1693-1701 (2001). Among the classes of knownRS domain containing proteins that may be used in the practice of theinvention are those listed in the table below.

In one embodiment of the invention, HIV Tat protein, or a fragmentthereof, can used as the transcription factor in a dominant negativefusion protein as described herein. The human Tat protein is an 86 aminoacid protein that is required efficient viral gene expression. The Tatsequence has been subdivided into several distinct regions based onstructure and function: a N-terminal activation region (amino acids1-19), a cysteine-rich domain (amino acids 20-31), a core region (aminoacids 32-47), a basic region (amino acids 48-57), and a glutamine-richregion (amino acids 60-76). See Karn, J. (ref). In one particularembodiment, a full length Tat is linked to the splicing factors SF1 orU2AF65. In another embodiment, the Tat activation domain (Tat AD) islinked to the splicing factors SF1 or U2AF65.

Generation of Nucleic Acids Encoding Dominant Negative Proteins

Dominant negative polypeptides and nucleic acids of the invention can bemade using routine techniques in the field of recombinant genetics.Basic texts disclosing the general methods of use in this inventioninclude Sambrook et al., Molecular Cloning, A Laboratory Manual (2nd ed.1989); Kriegler, Gene Transfer and Expression: A Laboratory Manual(1990); and Current Protocols in Molecular Biology (Ausubel et al.,eds., 1994)). In addition, essentially any nucleic acid can be customordered from any of a variety of commercial sources. Similarly, peptidesand antibodies can be custom ordered from any of a variety of commercialsources.

Expression Vectors for Nucleic Acids Encoding Dominant Negative Proteins

A nucleic acid encoding a dominant negative protein is typically clonedinto intermediate vectors for transformation into prokaryotic oreukaryotic cells for replication and/or expression. Intermediate vectorsare typically prokaryote vectors, e.g., plasmids, or shuttle vectors, orinsect vectors, for storage or manipulation of the nucleic acid encodingdominant negative proteins or production of protein. The nucleic acidencoding a dominant negative protein is also typically cloned into anexpression vector, for administration to a plant cell, animal cell,preferably a mammalian cell or a human cell, fungal cell, bacterialcell, or protozoal cell.

To obtain expression of a cloned gene or nucleic acid, a nucleic acidencoding a dominant negative protein is typically subcloned into anexpression vector that contains a promoter to direct transcription.Suitable bacterial and eukaryotic promoters are well known in the artand described, e.g., in Sambrook et al., Molecular Cloning, A LaboratoryManual (2nd ed. 1989); Kriegler, Gene Transfer and Expression: ALaboratory Manual (1990); and Current Protocols in Molecular Biology(Ausubel et al., eds., 1994). Bacterial expression systems forexpressing a dominant negative protein are available in, e.g., E. coli,Bacillus sp., and Salmonella (Palva et al., Gene 22:229-235 (1983)).Kits for such expression systems are commercially available. Eukaryoticexpression systems for mammalian cells, yeast, and insect cells are wellknown in the art and are also commercially available.

The promoter used to direct expression of a nucleic acid encoding adominant negative protein depends on the particular application. Forexample, a strong constitutive promoter is typically used for expressionand purification of a dominant negative protein. In contrast, when adominant negative protein is administered in vivo for gene regulation,either a constitutive or an inducible promoter is used, depending on theparticular use of the dominant negative protein. In addition, apreferred promoter for administration of a dominant negative protein canbe a weak promoter, such as HSV TK or a promoter having similaractivity. The promoter typically can also include elements that areresponsive to transactivation, e.g., hypoxia response elements, Gal4response elements, lac repressor response element, and small moleculecontrol systems such as tet-regulated systems and the RU-486 system(see, e.g., Gossen & Bujard, PNAS 89:5547 (1992); Oligino et al., GeneTher. 5:491-496 (1998); Wang et al., Gene Ther. 4:432-441 (1997);Neering et al., Blood 88:1147-1155 (1996); and Rendahl et al., Nat.Biotechnol. 16:757-761 (1998)).

In addition to the promoter, the expression vector typically contains atranscription unit or expression cassette that contains all theadditional elements required for the expression of the nucleic acid inhost cells, either prokaryotic or eukaryotic. A typical expressioncassette thus contains a promoter operably linked, e.g., to the nucleicacid sequence encoding the dominant negative protein, and signalsrequired, e.g., for efficient polyadenylation of the transcript,transcriptional termination, ribosome binding sites, or translationtermination. Additional elements of the cassette may include, e.g.,enhancers, and heterologous spliced intronic signals.

The particular expression vector used to transport the geneticinformation into the cell is selected with regard to the intended use ofthe dominant negative protein, e.g., expression in plants, animals,bacteria, fungus, protozoa etc. (see expression vectors describedbelow). Standard bacterial expression vectors include plasmids such aspBR322 based plasmids, pSKF, pET23D, and commercially available fusionexpression systems such as GST and LacZ. A preferred fusion protein isthe maltose binding protein, “MBP.” Such fusion proteins are used forpurification of the dominant negative protein. Epitope tags can also beadded to recombinant proteins to provide convenient methods ofisolation, for monitoring expression, and for monitoring cellular andsubcellular localization, e.g., c-myc or FLAG.

Expression vectors containing regulatory elements from eukaryoticviruses are often used in eukaryotic expression vectors, e.g., SV40vectors, papilloma virus vectors, and vectors derived from Epstein-Barrvirus. Other exemplary eukaryotic vectors include pMSG, pAV009/A+,pMTO10/A+, pMAMneo-5, baculovirus pDSVE, and any other vector allowingexpression of proteins under the direction of the SV40 early promoter,SV40 late promoter, metallothionein promoter, murine mammary tumor viruspromoter, Rous sarcoma virus promoter, polyhedrin promoter, or otherpromoters shown effective for expression in eukaryotic cells.

Some expression systems have markers for selection of stably transfectedcell lines such as thymidine kinase, hygromycin B phosphotransferase,and dihydrofolate reductase. High yield expression systems are alsosuitable, such as using a baculovirus vector in insect cells, with adominant negative protein encoding sequence under the direction of thepolyhedrin promoter or other strong baculovirus promoters.

The elements that are typically included in expression vectors alsoinclude a replicon that functions in E. coli, a gene encoding antibioticresistance to permit selection of bacteria that harbor recombinantplasmids, and unique restriction sites in nonessential regions of theplasmid to allow insertion of recombinant sequences.

Standard transfection methods are used to produce bacterial, mammalian,yeast or insect cell lines that express large quantities of protein,which are then purified using standard techniques (see, e.g., Colley etal., J. Biol. Chem. 264:17619-17622 (1989); Guide to ProteinPurification, in Methods in Enzymology, vol. 182 (Deutscher, ed.,1990)). Transformation of eukaryotic and prokaryotic cells are performedaccording to standard techniques (see, e.g., Morrison, J. Bact.132:349-351 (1977); Clark-Curtiss & Curtiss, Methods in Enzymology101:347-362 (Wu et al., eds, 1983).

Any of the well known procedures for introducing foreign nucleotidesequences into host cells may be used. These include the use of calciumphosphate transfection, polybrene, protoplast fusion, electroporation,liposomes, microinjection, naked DNA, plasmid vectors, viral vectors,both episomal and integrative, and any of the other well known methodsfor introducing cloned genomic DNA, cDNA, synthetic DNA or other foreigngenetic material into a host cell (see, e.g., Sambrook et al., supra).It is only necessary that the particular genetic engineering procedureused be capable of successfully introducing at least one gene into thehost cell capable of expressing the protein of choice.

Assays for Determining Regulation of Gene Expression by DominantNegative Proteins

A variety of assays can be used to determine the level of geneexpression regulation by dominant negative proteins. The activity of aparticular dominant negative protein can be assessed using a variety ofin vitro and in vivo assays, by measuring, e.g., protein or MRNA levels,product levels, enzyme activity, tumor growth; transcriptionalactivation or repression of a reporter gene such as a fluorescentprotein (e.g., GFP); second messenger levels (e.g., cGMP, cAMP, IP3,DAG, Ca²⁺); cytokine and hormone production levels; andneovascularization, using, e.g., immunoassays (e.g., ELISA andimmunohistochemical assays with antibodies), hybridization assays (e.g.,RNase protection, northerns, in situ hybridization, oligonucleotidearray studies), colorimetric assays, amplification assays, enzymeactivity assays, tumor growth assays, phenotypic assays, and the like.

Dominant negative proteins are typically first tested for activity invitro using cultured cells, e.g., 293 cells, CHO cells, VERO cells, BHKcells, HeLa cells, COS cells, and the like. Preferably, human cells areused. The dominant negative protein is often first tested using atransient expression system with a reporter gene, and then regulation ofthe target endogenous gene is tested in cells and in animals, both invivo and ex vivo. The dominant negative protein can be recombinantlyexpressed in a cell, recombinantly expressed in cells transplanted intoan animal, or recombinantly expressed in a transgenic animal, as well asadministered as a protein to an animal or cell using delivery vehiclesdescribed below. The cells can be immobilized, be in solution, beinjected into an animal, or be naturally occurring in a transgenic ornon-transgenic animal.

Modulation of gene expression is tested using one of the in vitro or invivo assays described herein. Samples or assays are treated with adominant negative protein and compared to control samples without thetest compound, to examine the extent of modulation.

The effects of the dominant negative proteins can be measured byexamining any of the parameters described above. Any suitable geneexpression, phenotypic, or physiological change can be used to assessthe influence of a dominant negative protein. When the functionalconsequences are determined using intact cells or animals, one can alsomeasure a variety of effects such as tumor growth, neovascularization,hormone release, transcriptional changes to both known anduncharacterized genetic markers (e.g., northern blots or oligonucleotidearray studies), changes in cell metabolism such as cell growth or pHchanges, and changes in intracellular second messengers such as cGMP.

Assays for dominant negative protein regulation of endogenous geneexpression can be performed in vitro. In one preferred in vitro assayformat, dominant negative protein regulation of endogenous geneexpression in cultured cells is measured by examining protein productionusing an ELISA assay (see Examples VI and VII). The test sample iscompared to control cells treated with an empty vector or an unrelateddominant negative protein that is targeted to another gene.

In another embodiment, dominant negative protein regulation ofendogenous gene expression is determined in vitro by measuring the levelof target gene mRNA expression. The level of gene expression is measuredusing amplification, e.g., using PCR, LCR, or hybridization assays,e.g., northern hybridization, RNase protection, dot blotting. RNaseprotection is used in one embodiment (see Example VIII and FIG. 10). Thelevel of protein or mRNA is detected using directly or indirectlylabeled detection agents, e.g., fluorescently or radioactively labelednucleic acids, radioactively or enzymatically labeled antibodies, andthe like, as described herein.

Alternatively, a reporter gene system can be devised using the targetgene promoter operably linked to a reporter gene such as luciferase,green fluorescent protein, CAT, or β-gal. The reporter construct istypically co-transfected into a cultured cell. After treatment with thedominant negative protein of choice, the amount of reporter genetranscription, translation, or activity is measured according tostandard techniques known to those of skill in the art.

Another example of an assay format useful for monitoring dominantnegative protein regulation of endogenous gene expression is performedin vivo. This assay is particularly useful for examining dominantnegative proteins that inhibit expression of tumor promoting genes,genes involved in tumor support, such as neovascularization (e.g.,VEGF), or that activate tumor suppressor genes such as p53. In thisassay, cultured tumor cells expressing the dominant negative protein ofchoice are injected subcutaneously into an immune compromised mouse suchas an athymic mouse, an irradiated mouse, or a SCID mouse. After asuitable length of time, preferably 4-8 weeks, tumor growth is measured,e.g., by volume or by its two largest dimensions, and compared to thecontrol. Tumors that have statistically significant reduction (using,e.g., Student's T test) are said to have inhibited growth.Alternatively, the extent of tumor neovascularization can also bemeasured. Immunoassays using endothelial cell specific antibodies areused to stain for vascularization of the tumor and the number of vesselsin the tumor. Tumors that have a statistically significant reduction inthe number of vessels (using, e.g., Student's T test) are said to haveinhibited neovascularization.

Transgenic and non-transgenic animals are also used as a preferredembodiment for examining regulation of endogenous gene expression invivo. Transgenic animals typically express the dominant negative proteinof choice. Alternatively, animals that transiently express the dominantnegative protein of choice, or to which the dominant negative proteinhas been administered in a delivery vehicle, can be used. Regulation ofendogenous gene expression is tested using any one of the assaysdescribed herein.

Nucleic Acids Encoding Dominant Negative Proteins and Gene Therapy

Conventional viral and non-viral based gene transfer methods can be usedto introduce nucleic acids encoding engineered dominant negativeproteins in mammalian cells or target tissues. Such methods can be usedto administer nucleic acids encoding dominant negative proteins to cellsin vitro. Preferably, the nucleic acids encoding dominant negativeproteins are administered for in vivo or ex vivo gene therapy uses.Non-viral vector delivery systems include DNA plasmids, naked nucleicacid, and nucleic acid complexed with a delivery vehicle such as aliposome. Viral vector delivery systems include DNA and RNA viruses,which have either episomal or integrated genomes after delivery to thecell. For a review of gene therapy procedures, see Anderson, Science256:808-813 (1992); Nabel & Felgner, TIBTECH 11:211-217 (1993); Mitani &Caskey, TIBTECH 11:162-166 (1993); Dillon, TIBTECH 11:167-175 (1993);Miller, Nature 357:455-460 (1992); Van Brunt, Biotechnology6(10):1149-1154 (1988); Vigne, Restorative Neurology and Neuroscience8:35-36 (1995); Kremer & Perricaudet, British Medical Bulletin51(1):31-44 (1995); Haddada et al., in Current Topics in Microbiologyand Immunology Doerfler and Bohm (eds) (1995); and Yu et al., GeneTherapy 1:13-26 (1994).

Methods of non-viral delivery of nucleic acids encoding engineereddominant negative proteins include lipofection, microinjection,ballistics, virosomes, liposomes, immunoliposomes, polycation orlipid:nucleic acid conjugates, naked DNA, artificial virions, andagent-enhanced uptake of DNA. Lipofection is described in e.g., U.S.Pat. No. 5,049,386, U.S. Pat. No. 4,946,787; and U.S. Pat. No.4,897,355) and lipofection reagents are sold commercially (e.g.,Transfectam™ and Lipofectin™). Cationic and neutral lipids that aresuitable for efficient receptor-recognition lipofection ofpolynucleotides include those of Felgner, WO 91/17424, WO 91/16024.Delivery can be to cells (ex vivo administration) or target tissues (invivo administration).

The preparation of lipid:nucleic acid complexes, including targetedliposomes such as immunolipid complexes, is well known to one of skillin the art (see, e.g., Crystal, Science 270:404-410 (1995); Blaese etal., Cancer Gene Ther. 2:291-297 (1995); Behr et al., Bioconjugate Chem.5:382-389 (1994); Remy et al., Bioconjugate Chem. 5:647-654 (1994); Gaoet al., Gene Therapy 2:710-722 (1995); Ahmad et al., Cancer Res.52:4817-4820 (1992); U.S. Pat. Nos. 4,186,183, 4,217,344, 4,235,871,4,261,975, 4,485,054, 4,501,728, 4,774,085, 4,837,028, and 4,946,787).

The use of RNA or DNA viral based systems for the delivery of nucleicacids encoding engineered dominant negative protein take advantage ofhighly evolved processes for targeting a virus to specific cells in thebody and trafficking the viral payload to the nucleus. Viral vectors canbe administered directly to patients (in vivo) or they can be used totreat cells in vitro and the modified cells are administered to patients(ex vivo). Conventional viral based systems for the delivery of dominantnegative proteins could include retroviral, lentivirus, adenoviral,adeno-associated and herpes simplex virus vectors for gene transfer.Viral vectors are currently the most efficient and versatile method ofgene transfer in target cells and tissues. Integration in the hostgenome is possible with the retrovirus, lentivirus, and adeno-associatedvirus gene transfer methods, often resulting in long term expression ofthe inserted transgene. Additionally, high transduction efficiencieshave been observed in many different cell types and target tissues.

The tropism of a retrovirus can be altered by incorporating foreignenvelope proteins, expanding the potential target population of targetcells. Lentiviral vectors are retroviral vector that are able totransduce or infect non-dividing cells and typically produce high viraltiters. Selection of a retroviral gene transfer system would thereforedepend on the target tissue. Retroviral vectors are comprised ofcis-acting long terminal repeats with packaging capacity for up to 6-10kb of foreign sequence. The minimum cis-acting LTRs are sufficient forreplication and packaging of the vectors, which are then used tointegrate the therapeutic gene into the target cell to provide permanenttransgene expression. Widely used retroviral vectors include those basedupon murine leukemia virus (MuLV), gibbon ape leukemia virus (GaLV),Simian Immuno deficiency virus (SIV), human immuno deficiency virus(HIV), and combinations thereof (see, e.g., Buchscher et al., J. Virol.66:2731-2739 (1992); Johann et al., J. Virol. 66:1635-1640 (1992);Sommerfelt et al., Virol. 176:58-59 (1990); Wilson et al., J. Virol.63:2374-2378 (1989); Miller et al., J. Virol. 65:2220-2224 (1991);PCT/US94/05700).

In applications where transient expression of the dominant negativeprotein is preferred, adenoviral based systems are typically used.Adenoviral based vectors are capable of very high transductionefficiency in many cell types and do not require cell division. Withsuch vectors, high titer and levels of expression have been obtained.This vector can be produced in large quantities in a relatively simplesystem. Adeno-associated virus (“AAV”) vectors are also used totransduce cells with target nucleic acids, e.g., in the in vitroproduction of nucleic acids and peptides, and for in vivo and ex vivogene therapy procedures (see, e.g., West et al., Virology 160:38-47(1987); U.S. Pat. No. 4,797,368; WO 93/24641; Kotin, Human Gene Therapy5:793-801 (1994); Muzyczka, J. Clin. Invest. 94:1351 (1994).Construction of recombinant AAV vectors are described in a number ofpublications, including U.S. Pat. No. 5,173,414; Tratschin et al., Mol.Cell. Biol. 5:3251-3260 (1985); Tratschin, et al., Mol. Cell. Biol.4:2072-2081 (1984); Hermonat & Muzyczka, PNAS 81:6466-6470 (1984); andSamulski et al., J. Virol. 63:03822-3828 (1989).

In particular, at least six viral vector approaches are currentlyavailable for gene transfer in clinical trials, with retroviral vectorsby far the most frequently used system. All of these viral vectorsutilize approaches that involve complementation of defective vectors bygenes inserted into helper cell lines to generate the transducing agent.

pLASN and MFG-S are examples are retroviral vectors that have been usedin clinical trials (Dunbar et al., Blood 85:3048-305 (1995); Kohn etal., Nat. Med. 1:1017-102 (1995); Malech et al., PNAS 94:22 12133-12138(1997)). PA317/pLASN was the first therapeutic vector used in a genetherapy trial. (Blaese et al., Science 270:475-480 (1995)). Transductionefficiencies of 50% or greater have been observed for MFG-S packagedvectors. (Ellem et al., Immunol Immunother. 44(1):10-20 (1997); Dranoffet al., Hum. Gene Ther. 1:111-2(1997).

Recombinant adeno-associated virus vectors (rAAV) are a promisingalternative gene delivery systems based on the defective andnonpathogenic parvovirus adeno-associated type 2 virus. All vectors arederived from a plasmid that retains only the AAV 145 bp invertedterminal repeats flanking the transgene expression cassette. Efficientgene transfer and stable transgene delivery due to integration into thegenomes of the transduced cell are key features for this vector system.(Wagner et al., Lancet 351:9117 1702-3 (1998), Kearns et al., Gene Ther.9:748-55 (1996)).

Replication-deficient recombinant adenoviral vectors (Ad) arepredominantly used for colon cancer gene therapy, because they can beproduced at high titer and they readily infect a number of differentcell types. Most adenovirus vectors are engineered such that a transgenereplaces the Ad E1a, E1b, and E3 genes; subsequently the replicationdefector vector is propagated in human 293 cells that supply deletedgene function in trans. Ad vectors can transduce multiply types oftissues in vivo, including nondividing, differentiated cells such asthose found in the liver, kidney and muscle system tissues. ConventionalAd vectors have a large carrying capacity. An example of the use of anAd vector in a clinical trial involved polynucleotide therapy forantitumor immunization with intramuscular injection (Sterman et al.,Hum. Gene Ther. 7:1083-9 (1998)). Additional examples of the use ofadenovirus vectors for gene transfer in clinical trials includeRosenecker et al., Infection 24:1 5-10 (1996); Sterman et al., Hum. GeneTher. 9:7 1083-1089 (1998); Welsh et al., Hum. Gene Ther. 2:205-18(1995); Alvarez et al., Hum. Gene Ther. 5:597-613 (1997); Topf et al.,Gene Ther. 5:507-513 (1998); Sterman et al., Hum. Gene Ther. 7:1083-1089(1998).

Packaging cells are used to form virus particles that are capable ofinfecting a host cell. Such cells include 293 cells, which packageadenovirus, and ψ2 cells or PA317 cells, which package retrovirus. Viralvectors used in gene therapy are usually generated by producer cell linethat packages a nucleic acid vector into a viral particle. The vectorstypically contain the minimal viral sequences required for packaging andsubsequent integration into a host, other viral sequences being replacedby an expression cassette for the protein to be expressed. The missingviral functions are supplied in trans by the packaging cell line. Forexample, AAV vectors used in gene therapy typically only possess ITRsequences from the AAV genome which are required for packaging andintegration into the host genome. Viral DNA is packaged in a cell line,which contains a helper plasmid encoding the other AAV genes, namely repand cap, but lacking ITR sequences. The cell line is also infected withadenovirus as a helper. The helper virus promotes replication of the AAVvector and expression of AAV genes from the helper plasmid. The helperplasmid is not packaged in significant amounts due to a lack of ITRsequences. Contamination with adenovirus can be reduced by, e.g., heattreatment to which adenovirus is more sensitive than AAV.

In many gene therapy applications, it is desirable that the gene therapyvector be delivered with a high degree of specificity to a particulartissue type. A viral vector is typically modified to have specificityfor a given cell type by expressing a ligand as a fusion protein with aviral coat protein on the viruses outer surface. The ligand is chosen tohave affinity for a receptor known to be present on the cell type ofinterest. For example, Han et al., PNAS 92:9747-9751 (1995), reportedthat Moloney murine leukemia virus can be modified to express humanheregulin fused to gp70, and the recombinant virus infects certain humanbreast cancer cells expressing human epidermal growth factor receptor.This principle can be extended to other pairs of virus expressing aligand fusion protein and target cell expressing a receptor. Forexample, filamentous phage can be engineered to display antibodyfragments (e.g., FAB or Fv) having specific binding affinity forvirtually any chosen cellular receptor. Although the above descriptionapplies primarily to viral vectors, the same principles can be appliedto nonviral vectors. Such vectors can be engineered to contain specificuptake sequences thought to favor uptake by specific target cells.

Gene therapy vectors can be delivered in vivo by administration to anindividual patient, typically by systemic administration (e.g.,intravenous, intraperitoneal, intramuscular, subdermal, or intracranialinfusion) or topical application, as described below. Alternatively,vectors can be delivered to cells ex vivo, such as cells explanted froman individual patient (e.g., lymphocytes, bone marrow aspirates, tissuebiopsy) or universal donor hematopoietic stem cells, followed byreimplantation of the cells into a patient, usually after selection forcells which have incorporated the vector.

Ex vivo cell transfection for diagnostics, research, or for gene therapy(e.g., via re-infusion of the transfected cells into the host organism)is well known to those of skill in the art. In a preferred embodiment,cells are isolated from the subject organism, transfected with adominant negative protein nucleic acid (gene or cDNA), and re-infusedback into the subject organism (e.g., patient). Various cell typessuitable for ex vivo transfection are well known to those of skill inthe art (see, e.g., Freshney et al., Culture of Animal Cells, A Manualof Basic Technique (3rd ed. 1994)) and the references cited therein fora discussion of how to isolate and culture cells from patients).

In one embodiment, stem cells are used in ex vivo procedures for celltransfection and gene therapy. The advantage to using stem cells is thatthey can be differentiated into other cell types in vitro, or can beintroduced into a mammal (such as the donor of the cells) where theywill engraft in the bone marrow. Methods for differentiating CD34+ cellsin vitro into clinically important immune cell types using cytokinessuch a GM-CSF, IFN-γ and TNF-α are known (see Inaba et al., J. Exp. Med.176:1693-1702 (1992)).

Stem cells are isolated for transduction and differentiation using knownmethods. For example, stem cells are isolated from bone marrow cells bypanning the bone marrow cells with antibodies which bind unwanted cells,such as CD4+ and CD8+ (T cells), CD45+ (panB cells), GR-1(granulocytes), and Iad (differentiated antigen presenting cells) (seeInaba et al., J. Exp. Med. 176:1693-1702 (1992)).

Vectors (e.g., retroviruses, adenoviruses, liposomes, etc.) containingtherapeutic dominant negative protein nucleic acids can be alsoadministered directly to the organism for transduction of cells in vivo.Alternatively, naked DNA can be administered. Administration is by anyof the routes normally used for introducing a molecule into ultimatecontact with blood or tissue cells. Suitable methods of administeringsuch nucleic acids are available and well known to those of skill in theart, and, although more than one route can be used to administer aparticular composition, a particular route can often provide a moreimmediate and more effective reaction than another route.

Pharmaceutically acceptable carriers are determined in part by theparticular composition being administered, as well as by the particularmethod used to administer the composition. Accordingly, there is a widevariety of suitable formulations of pharmaceutical compositions of thepresent invention, as described below (see, e.g., Remington 'sPharmaceutical Sciences, 17th ed., 1989).

Delivery Vehicles for Dominant Negative Proteins

An important factor in the administration of polypeptide compounds, suchas the dominant negative proteins of the present invention, is ensuringthat the polypeptide has the ability to traverse the plasma membrane ofa cell, or the membrane of an intra-cellular compartment such as thenucleus. Cellular membranes are composed of lipid-protein bilayers thatare freely permeable to small, nonionic lipophilic compounds and areinherently impermeable to polar compounds, macromolecules, andtherapeutic or diagnostic agents. However, proteins and other compoundssuch as liposomes have been described, which have the ability totranslocate polypeptides such as dominant negative proteins across acell membrane.

For example, “membrane translocation polypeptides” have amphiphilic orhydrophobic amino acid subsequences that have the ability to act asmembrane-translocating carriers. In one embodiment, homeodomain proteinshave the ability to translocate across cell membranes. The shortestinternalizable peptide of a homeodomain protein, Antennapedia, was foundto be the third helix of the protein, from amino acid position 43 to 58(see, e.g., Prochiantz, Current Opinion in Neurobiology 6:629-634(1996)). Another subsequence, the h (hydrophobic) domain of signalpeptides, was found to have similar cell membrane translocationcharacteristics (see, e.g., Lin et al., J. Biol. Chem. 270:1 4255-14258(1995)).

Examples of peptide sequences which can be linked to a dominant negativeprotein of the invention, for facilitating uptake of dominant negativeprotein into cells, include, but are not limited to: an 11 amino acidpeptide of the tat protein of HIV; a 20 residue peptide sequence whichcorresponds to amino acids 84-103 of the p16 protein (see Fahraeus etal., Current Biology 6:84 (1996)); the third helix of the 60-amino acidlong homeodomain of Antennapedia (Derossi et al., J. Biol. Chem.269:10444 (1994)); the h region of a signal peptide such as the Kaposifibroblast growth factor (K-FGF) h region (Lin et al., supra); or theVP22 translocation domain from HSV (Elliot & O'Hare, Cell 88:223-233(1997)). Other suitable chemical moieties that provide enhanced cellularuptake may also be chemically linked to dominant negative proteins. Forexample, nuclear localization signals may be appended to enhance uptakeinto the nuclear compartment of cells.

Toxin molecules also have the ability to transport polypeptides acrosscell membranes. Often, such molecules are composed of at least two parts(called “binary toxins”): a translocation or binding domain orpolypeptide and a separate toxin domain or polypeptide. Typically, thetranslocation domain or polypeptide binds to a cellular receptor, andthen the toxin is transported into the cell. Several bacterial toxins,including Clostridium perfringens iota toxin, diphtheria toxin (DT),Pseudomonas exotoxin A (PE), pertussis toxin (PT), Bacillus anthracistoxin, and pertussis adenylate cyclase (CYA), have been used in attemptsto deliver peptides to the cell cytosol as internal or amino-terminalfusions (Arora et al., J. Biol. Chem., 268:3334-3341 (1993); Perelle etal., Infect. Immun., 61:5147-5156 (1993); Stenmark et al., J. Cell Biol.113:1025-1032 (1991); Donnelly et al., PNAS 90:3530-3534 (1993);Carbonetti et al., Abstr. Annu. Meet. Am. Soc. Microbiol. 95:295 (1995);Sebo et al., Infect. Immun. 63:3851-3857 (1995); Klimpel et al., PNASU.S.A. 89:10277-10281 (1992); and Novak et al., J. Biol. Chem.267:17186-17193 1992)).

Such subsequences can be used to translocate dominant negative proteinsacross a cell membrane. Dominant negative proteins can be convenientlyfused to or derivatized with such sequences. Typically, thetranslocation sequence is provided as part of a fusion protein.Optionally, a linker can be used to link the dominant negative proteinand the translocation sequence. Any suitable linker can be used, e.g., apeptide linker.

The dominant negative protein can also be introduced into an animalcell, preferably a mammalian cell, via a liposomes and liposomederivatives such as immunoliposomes. The term “liposome” refers tovesicles comprised of one or more concentrically ordered lipid bilayers,which encapsulate an aqueous phase. The aqueous phase typically containsthe compound to be delivered to the cell, i.e., a dominant negativeprotein.

The liposome fuses with the plasma membrane, thereby releasing the druginto the cytosol. Alternatively, the liposome is phagocytosed or takenup by the cell in a transport vesicle. Once in the endosome orphagosome, the liposome either degrades or fuses with the membrane ofthe transport vesicle and releases its contents.

In current methods of drug delivery via liposomes, the liposomeultimately becomes permeable and releases the encapsulated compound (inthis case, a dominant negative protein) at the target tissue or cell.For systemic or tissue specific delivery, this can be accomplished, forexample, in a passive manner wherein the liposome bilayer degrades overtime through the action of various agents in the body. Alternatively,active drug release involves using an agent to induce a permeabilitychange in the liposome vesicle. Liposome membranes can be constructed sothat they become destabilized when the environment becomes acidic nearthe liposome membrane (see, e.g., PNAS 84:7851 (1987); Biochemistry28:908 (1989)). When liposomes are endocytosed by a target cell, forexample, they become destabilized and release their contents. Thisdestabilization is termed fusogenesis. Dioleoylphosphatidylethanolamine(DOPE) is the basis of many “fusogenic” systems.

Such liposomes typically comprise a dominant negative protein and alipid component, e.g., a neutral and/or cationic lipid, optionallyincluding a receptor-recognition molecule such as an antibody that bindsto a predetermined cell surface receptor or ligand (e.g., an antigen). Avariety of methods are available for preparing liposomes as describedin, e.g., Szoka et al., Ann. Rev. Biophys. Bioeng. 9:467 (1980), U.S.Pat. Nos. 4,186,183, 4,217,344, 4,235,871, 4,261,975, 4,485,054,4,501,728, 4,774,085, 4,837,028, 4,235,871, 4,261,975, 4,485,054,4,501,728, 4,774,085, 4,837,028, 4,946,787, PCT Publication No. WO91\17424, Deamer & Bangham, Biochim. Biophys. Acta 443:629-634 (1976);Fraley, et al., PNAS 76:3348-3352 (1979); Hope et al., Biochim. Biophys.Acta 812:55-65 (1985); Mayer et al., Biochim. Biophys. Acta 858:161-168(1986); Williams et al., PNAS 85:242-246 (1988); Liposomes (Ostro (ed.),1983, Chapter 1); Hope et al., Chem. Phys. Lip. 40:89 (1986);Gregoriadis, Liposome Technology (1984) and Lasic, Liposomes: fromPhysics to Applications (1993)). Suitable methods include, for example,sonication, extrusion, high pressure/homogenization, microfluidization,detergent dialysis, calcium-induced fusion of small liposome vesiclesand ether-fusion methods, all of which are well known in the art.

In certain embodiments of the present invention, it is desirable totarget the liposomes of the invention using targeting moieties that arespecific to a particular cell type, tissue, and the like. Targeting ofliposomes using a variety of targeting moieties (e.g., ligands,receptors, and monoclonal antibodies) has been previously described(see, e.g., U.S. Pat. Nos. 4,957,773 and 4,603,044).

Examples of targeting moieties include monoclonal antibodies specific toantigens associated with neoplasms, such as prostate cancer specificantigen and MAGE. Tumors can also be diagnosed by detecting geneproducts resulting from the activation or over-expression of oncogenes,such as ras or c-erbB2. In addition, many tumors express antigensnormally expressed by fetal tissue, such as the alphafetoprotein (AFP)and carcinoembryonic antigen (CEA). Sites of viral infection can bediagnosed using various viral antigens such as hepatitis B core andsurface antigens (HBVc, HBVs) hepatitis C antigens, Epstein-Barr virusantigens, human immunodeficiency type-1 virus (HIV1) and papilloma virusantigens. Inflammation can be detected using molecules specificallyrecognized by surface molecules which are expressed at sites ofinflammation such as integrins (e.g., VCAM-1), selectin receptors (e.g.,ELAM-1) and the like.

Standard methods for coupling targeting agents to liposomes can be used.These methods generally involve incorporation into liposomes lipidcomponents, e.g., phosphatidylethanolamine, which can be activated forattachment of targeting agents, or derivatized lipophilic compounds,such as lipid derivatized bleomycin. Antibody targeted liposomes can beconstructed using, for instance, liposomes which incorporate protein A(see Renneisen et al., J. Biol. Chem., 265:16337-16342 (1990) andLeonetti et al., PNAS 87:2448-2451 (1990).

Doses of Dominant Negative Proteins

For therapeutic applications of dominant negative proteins, the doseadministered to a patient, in the context of the present inventionshould be sufficient to effect a beneficial therapeutic response in thepatient over time. In addition, particular dosage regimens can be usefulfor determining phenotypic changes in an experimental setting, e.g., infunctional genomics studies, and in cell or animal models. The dose willbe determined by the condition of the patient, as well as the bodyweight or surface area of the patient to be treated. The size of thedose also will be determined by the existence, nature, and extent of anyadverse side-effects that accompany the administration of a particularcompound or vector in a particular patient.

The appropriate dose of an expression vector encoding a dominantnegative protein can also be calculated by taking into account theaverage rate of dominant negative protein expression from the promoterand the average rate of dominant negative protein degradation in thecell. Preferably, a weak promoter such as a wild-type or mutant HSV TKis used.

In determining the effective amount of a dominant negative protein to beadministered in the treatment or prophylaxis of disease, the physicianevaluates circulating plasma levels of the dominant negative protein ornucleic acid encoding the dominant negative protein, potential dominantnegative protein toxicities, progression of the disease, and theproduction of anti-dominant negative protein antibodies. Administrationcan be accomplished via single or divided doses.

Pharmaceutical Compositions and Administration

Dominant negative proteins and expression vectors encoding dominantnegative proteins can be administered directly to the patient formodulation of gene expression and for therapeutic or prophylacticapplications, for example, cancer, ischemia, diabetic retinopathy,macular degeneration, rheumatoid arthritis, psoriasis, HIV infection,sickle cell anemia, Alzheimer's disease, muscular dystrophy,neurodegenerative diseases, vascular disease, cystic fibrosis, stroke,and the like. Examples of microorganisms that can be inhibited bydominant negative protein gene therapy include pathogenic bacteria,e.g., chlamydia, rickettsial bacteria, mycobacteria, staphylococci,streptococci, pneumococci, meningococci and conococci, klebsiella,proteus, serratia, pseudomonas, legionella, diphtheria, salmonella,bacilli, cholera, tetanus, botulism, anthrax, plague, leptospirosis, andLyme disease bacteria; infectious fungus, e.g., Aspergillus, Candidaspecies; protozoa such as sporozoa (e.g., Plasmodia), rhizopods (e.g.,Entamoeba) and flagellates (Trypanosoma, Leishmania, Trichomonas,Giardia, etc.);viral diseases, e.g., hepatitis (A, B, or C), herpesvirus (e.g., VZV, HSV-1, HSV-6, HSV-II, CMV, and EBV), HIV, Ebola,adenovirus, influenza virus, flaviviruses, echovirus, rhinovirus,coxsackie virus, coronavirus, respiratory syncytial virus, mumps virus,rotavirus, measles virus, rubella virus, parvovirus, vaccinia virus,HTLV virus, dengue virus, papillomavirus, poliovirus, rabies virus, andarboviral encephalitis virus, etc.

Administration of therapeutically effective amounts is by any of theroutes normally used for introducing dominant negative protein intoultimate contact with the tissue to be treated. The dominant negativeproteins are administered in any suitable manner, preferably withpharmaceutically acceptable carriers. Suitable methods of administeringsuch modulators are available and well known to those of skill in theart, and, although more than one route can be used to administer aparticular composition, a particular route can often provide a moreimmediate and more effective reaction than another route.

Pharmaceutically acceptable carriers are determined in part by theparticular composition being administered, as well as by the particularmethod used to administer the composition. Accordingly, there is a widevariety of suitable formulations of pharmaceutical compositions of thepresent invention (see, e.g., Remington's Pharmaceutical Sciences,17^(th) ed. 1985)).

The dominant negative proteins, alone or in combination with othersuitable components, can be made into aerosol formulations (i.e., theycan be “nebulized”) to be administered via inhalation. Aerosolformulations can be placed into pressurized acceptable propellants, suchas dichlorodifluoromethane, propane, nitrogen, and the like.

Formulations suitable for parenteral administration, such as, forexample, by intravenous, intramuscular, intradermal, and subcutaneousroutes, include aqueous and non-aqueous, isotonic sterile injectionsolutions, which can contain antioxidants, buffers, bacteriostats, andsolutes that render the formulation isotonic with the blood of theintended recipient, and aqueous and non-aqueous sterile suspensions thatcan include suspending agents, solubilizers, thickening agents,stabilizers, and preservatives. In the practice of this invention,compositions can be administered, for example, by intravenous infusion,orally, topically, intraperitoneally, intravesically or intrathecally.The formulations of compounds can be presented in unit-dose ormulti-dose sealed containers, such as ampules and vials. Injectionsolutions and suspensions can be prepared from sterile powders,granules, and tablets of the kind previously described.

Functional Genomics Assays

Dominant negative proteins also have use for assays to determine thephenotypic consequences and function of gene expression. The recentadvances in analytical techniques, coupled with focussed mass sequencingefforts have created the opportunity to identify and characterize manymore molecular targets than were previously available. This newinformation about genes and their functions will speed along basicbiological understanding and present many new targets for therapeuticintervention. In some cases analytical tools have not kept pace with thegeneration of new data. An example is provided by recent advances in themeasurement of global differential gene expression. These methods,typified by gene expression microarrays, differential cDNA cloningfrequencies, subtractive hybridization and differential display methods,can very rapidly identify genes that are up or down-regulated indifferent tissues or in response to specific stimuli. Increasingly, suchmethods are being used to explore biological processes such as,transformation, tumor progression, the inflammatory response,neurological disorders etc. One can now very easily generate long listsof differentially expressed genes that correlate with a givenphysiological phenomenon, but demonstrating a causative relationshipbetween an individual differentially expressed gene and the phenomenonis difficult. Until now, simple methods for assigning function todifferentially expressed genes have not kept pace with the ability tomonitor differential gene expression.

Using conventional molecular approaches, over expression of a candidategene can be accomplished by cloning a full-length cDNA, subcloning itinto a mammalian expression vector and transfecting the recombinantvector into an appropriate host cell. This approach is straightforwardbut labor intensive, particularly when the initial candidate gene isrepresented by a simple expressed sequence tag (EST). Under expressionof a candidate gene by “conventional” methods is yet more problematic.Antisense methods and methods that rely on targeted ribozymes areunreliable, succeeding for only a small fraction of the targetsselected. Gene knockout by homologous recombination works fairly well inrecombinogenic stem cells but very inefficiently in somatically derivedcell lines. In either case large clones of syngeneic genomic DNA (on theorder of 10 kb) should be isolated for recombination to workefficiently.

The dominant negative protein technology can be used to rapidly analyzedifferential gene expression studies. Engineered dominant negativeproteins can be readily used to up or down-regulate any endogenoustarget gene. This makes the dominant negative protein technology idealfor analysis of long lists of poorly characterized differentiallyexpressed genes.

This specific example of using engineered dominant negative proteins toadd functional information to genomic data is merely illustrative. Anyexperimental situation that could benefit from the specific up ordown-regulation of a gene or genes could benefit from the reliabilityand ease of use of engineered dominant negative proteins.

Additionally, greater experimental control can be imparted by dominantnegative proteins than can be achieved by more conventional methods.This is because the production and/or function of an engineered dominantnegative protein can be placed under small molecule control. Examples ofthis approach are provided by the Tet-On system, the ecdysone-regulatedsystem and a system incorporating a chimeric factor including a mutantprogesterone receptor. These systems are all capable of indirectlyimparting small molecule control on any endogenous gene of interest orany transgene by placing the function and/or expression of a dominantnegative protein under small molecule control.

Transgenic Mice

A further application of the dominant negative protein technology ismanipulating gene expression in transgenic animals. Conventionaldown-regulation of gene expression in transgenic animals is plagued bytechnical difficulties. Gene knockout by homologous recombination is themethod most commonly applied currently. This method requires arelatively long genomic clone of the gene to be knocked out (ca. 10 kb).Typically, a selectable marker is inserted into an exon of the gene ofinterest to effect the gene disruption, and a second counter-selectablemarker provided outside of the region of homology to select homologousversus non-homologous recombinants. This construct is transfected intoembryonic stem cells and recombinants selected in culture. Recombinantstem cells are combined with very early stage embryos generatingchimeric animals. If the chimerism extends to the germline homozygousknockout animals can be isolated by back-crossing. When the technologyis successfully applied, knockout animals can be generated inapproximately one year. Unfortunately two common issues often preventthe successful application of the knockout technology; embryoniclethality and developmental compensation. Embryonic lethality resultswhen the gene to be knocked out plays an essential role in development.This can manifest itself as a lack of chimerism, lack of germlinetransmission or the inability to generate homozygous back crosses. Genescan play significantly different physiological roles during developmentversus in adult animals. Therefore, embryonic lethality is notconsidered a rationale for dismissing a gene target as a useful targetfor therapeutic intervention in adults. Embryonic lethality most oftensimply means that the gene of interest can not be easily studied inmouse models, using conventional methods.

Developmental compensation is the substitution of a related gene productfor the gene product being knocked out. Genes often exist in extensivefamilies. Selection or induction during the course of development can insome cases trigger the substitution of one family member for anothermutant member. This type of functional substitution may not be possiblein the adult animal. A typical result of developmental compensationwould be the lack of a phenotype in a knockout mouse when the ablationof that gene's function in an adult would otherwise cause aphysiological change. This is a kind of false negative result that oftenconfounds the interpretation of conventional knockout mouse models.

A few new methods have been developed to avoid embryonic lethality.These methods are typified by an approach using the cre recombinase andlox DNA recognition elements. The recognition elements are inserted intoa gene of interest using homologous recombination (as described above)and the expression of the recombinase induced in adult micepost-development. This causes the deletion of a portion of the targetgene and avoids developmental complications. The method is laborintensive and suffers form chimerism due to non-uniform induction of therecombinase.

The use of engineered dominant negative proteins to manipulate geneexpression can be restricted to adult animals using the small moleculeregulated systems described in the previous section. Expression and/orfunction of a dominant negative protein can be switched off duringdevelopment and switched on at will in the adult animals. This approachrelies on the expression of the dominant negative protein only;homologous recombination is not required. Because the dominant negativeproteins are trans dominant, there is no concern about germlinetransmission or homozygosity. These issues dramatically affect the timeand labor required to go from a poorly characterized gene candidate (acDNA or EST clone) to a mouse model. This ability can be used to rapidlyidentify and/or validate gene targets for therapeutic intervention,generate novel model systems and permit the analysis of complexphysiological phenomena (development, hematopoiesis, transformation,neural function etc.). Chimeric targeted mice can be derived accordingto Hogan et al., Manipulating the Mouse Embryo: A Laboratory Manual,(1988); Teratocarcinomas and Embryonic Stem Cells: A Practical Approach,Robertson, ed., (1987); and Capecchi et al., Science 244:1288 (1989).

All publications and patent applications cited in this specification areherein incorporated by reference as if each individual publication orpatent application were specifically and individually indicated to beincorporated by reference.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it will be readily apparent to one of ordinary skill inthe art in light of the teachings of this invention that certain changesand modifications may be made thereto without departing from the spiritor scope of the appended claims.

EXAMPLES

The following examples are provided by way of illustration only and notby way of limitation. Those of skill in the art will readily recognize avariety of noncritical parameters that could be changed or modified toyield essentially similar results.

Example 1 Dominant Negative Inhibition of Transcription by Linking Tatto a Protein that Localizes to the Transcriptional Machinery

The Tat-hybrid assay, in which Tat fused to a heterologous RNA-bindingdomain (RBD) elicits activation of an HIV-1 LTR reporter plasmidcontaining a cognate RNA-binding site, has been useful for studyingRNA-protein interactions in living cells⁶. However, as with other typesof fusion protein assays, dominant negative proteins can be generatedunintentionally that score as false negatives. We discovered a novelclass of highly potent dominant negatives, exemplified by Tat fusions tosplicing factors, whose potency appears to be dictated bycotranscriptional recruitment to the HIV promoter.

We devised a dual-fluorescence Tat-hybrid assay to monitor RNA-bindingspecificity using two pairs of orthogonal reporters and Tat fusions,herein referred to as T-fusions. To calibrate the assay, T-BIV_(RBD) , afusion between the HIV Tat activation domain (AD) and the RBD of bovineimmunodeficiency virus (BIV) Tat, was used to activate a BIV TAR(BTAR)-DsRed reporter, while T-SF1, a Tat fusion to human splicingfactor SF1, was used to activate a branch point sequence (BPS)-GFPreporter (FIG. 1 a). When transfected on their own, both T-BIV_(RBD) andT-SF1 strongly activated only their cognate RNA reporters. Strikingly,however, activation via the T-BIV_(RBD)-BTAR interaction was stronglyinhibited when both T-fusions were co-transfected (3-fold activation)whereas activation via the T-SF1-BPS interaction was unaffected(170-fold).

Using a more quantitative luciferase reporter, we found that inhibitionwas remarkably potent, with a stoichiometric amount of T-SF1 plasmid DNA(5 ng) sufficient to almost completely block activation mediated by theBIV Tat-BTAR interaction (FIG. 1 b). The dose response of inhibition byT-SF1 mirrors activation of a BPS reporter (FIG. 1 b), demonstratingthat T-SF1 functions as an activator through its cognate RNA-bindingsite. We confirmed that the high potency observed in the transfectionexperiments accurately reflected relative protein stoichiometries byWestern blot analysis of HA-tagged Tat activator and dominant negativeproteins (FIG. 6). It is clear that the high potency results from thefusion, as SF1 alone does not inhibit Tat activation (data not shown)and it is known that the Tat AD without an RBD is a very weak dominantnegative^(4,5). Given that several splicing factors, including SF1 andU2AF65, interact with CTD-associated factors or directly with RNAP II⁷,we hypothesized that the SF1 moiety targets the T-fusion to RNAP II. Wepropose a model in which this recruitment step increases the localconcentration of the non-activating T-fusion at the HIV promoter therebyout-competing the wild-type Tat activator (see below).

If the targeting hypothesis is correct, then T-fusions to other RNAPII-localized splicing factors might show a similar phenotype. Indeed,T-U2AF65 is an even more potent inhibitor (FIG. 1 c, left panel). U2AF65fusions to either full-length Tat or the Tat AD are equally potent (FIG.5), showing that the Tat RBD is dispensable for the dominant negativefunction. T-U2AF65 also is a potent inhibitor of Tat activation whenmediated by the Rev-RRE IIB RNA interaction (FIG. 1 c, right panel),further demonstrating that the inhibitor functions independently of theRNA-protein interaction. The Tat AD alone is a poor inhibitor (FIG. 1c), again showing the requirement of the targeting moiety. Besidessplicing factors, other proteins interact with RNAP II before, during,or after pre-initiation complex (PIC) formation, including otherRNA-processing proteins that are co-transcriptionally recruited to theCTD². T-fusions to some, but not all, of these factors inhibitedTat-mediated activation to different extents, but none was as potent asT-U2AF65 (FIG. 7).

The specificity of inhibition for the HIV promoter was assessed bymeasuring effects of T-U2AF65 on other reporter-activator combinations.No inhibition was observed in any case, including activation by theP-TEFb-dependent MHC class II transactivator (CIITA) and heat-shockfactor 1 (HSF1), as well as p53 and GAL4-VP16, and constitutiveexpression from the cytomegalovirus (CMV) promoter (FIG. 1 d).Furthermore, no inhibition of cellular promoters was observed in stablecell lines expressing T-U2AF65 (FIG. 9).

Example 2 Effect of Localization of the Dominant Negative Protein onInhibition of Transcription

To begin examining the effect of localization on inhibitor activity, wefirst asked whether nuclear localization alone might account for some ofits potency, particularly because a variety of T-fusions showedactivity, albeit not as strong as T-U2AF65 (FIG. 7). We generatedT-fusions to GFP with or without a nuclear localization signal (NLS) andobserved very weak dominant negative activity for the AD fusion alone(T-GFP) and only slightly enhanced inhibition for T-NLS-GFP (FIG. 2 a).This result is consistent with the mild dominant negative phenotypeobserved for a Tat 1-53 truncation mutant that deletes part of theRNA-binding domain but still retains an NLS⁵. In contrast, T-U2AF65-GFPis a highly potent inhibitor (FIG. 2 a), indicating that nuclearlocalization is not the major factor contributing to potency. T-GFP isdistributed in the cytoplasm and nucleus, like unfused GFP, whereasT-NLS-GFP is greater than 95% nuclear and absent from the nucleolus, asexpected (FIG. 2 a). T-U2AF65-GFP shows a striking subnuclear pattern of“speckle-associated patches” (FIG. 2 a). Related patterns are seen withRS-domain containing proteins^(8,9), which include U2AF65, prompting usto examine the domains of T-U2AF65 important for inhibition.

The RS domains of U2AF65 and other splicing factors help recruit theseproteins to regions of active splicing within the nucleus^(8,9) and alsoare believed to interact with RNAP II during transcription complexassembly⁹. The presence of RNAP II and splicing and mRNA-export factorssuggests an active role for the “speckle-associated patches” in mRNAprocessing, although they are otherwise considered mainly as storagesites for factors involved in mRNA metabolisms^(10,11). To test thepossible involvement of RS domains in dominant negative inhibition, wegenerated a T-fusion lacking the RS domain (T-U2AF65ΔRS, which containsU2AF65 residues 91-475) and a second with the RS domain alone (T-RS,which contains U2AF65 residues 2-73). Of these, only T-RS remained apotent inhibitor (FIG. 2 b). T-RS shows a speckle pattern even morestriking than full-length T-U2AF65, with T-RS concentrated in only about10-30 speckles. To confirm that the Tat AD also is important forinhibition, we generated T-U2AF65 and T-RS mutants with a Lys41-to-Alasubstitution in the AD that disrupts interactions with transcriptionalco-activators, particularly P-TEFb¹². Both are inactive as inhibitorsdespite having the same localization patterns as the non-mutant versions(FIGS. 2 b and 8). U2AF65 RS-domain fusions to other transcriptionalADs, including VP16 and E1A, do not inhibit Tat-mediated activation(D'Orso and Frankel, unpublished observations), further demonstratingthe specificity of inhibition and the requirement for the Tat AD. Thus,both an RS domain and a functional Tat AD are necessary and sufficientto generate the potent dominant negative phenotype. We envisage a modelin which the U2AF65 RS-domain targets the T-fusion to subnuclearcompartments (speckles) where transcription complexes are assembling,thereby facilitating the interaction of the Tat AD with one or morefactors of the transcriptional machinery assembling at the HIV promoter.

Example 3 Recruitment of the Dominant Negative Protein to theTranscriptional Machinery

To examine the recruitment of T-U2AF65 to the transcriptional machinery,we first analyzed possible interactions with RNAP II byco-immunoprecipitation using antibodies against the Ser5-phosphorylatedCTD (Ser5P-CTD), known as RNAP IIa. T-U2AF65-GFP, as well as the K41ATat AD mutant, are complexed with RNAP IIa in a RNA-independent manner(FIG. 3 a). Strikingly, no interaction is seen with T-NLS-GFP lackingthe U2AF65 moiety despite the reported interaction of Tat with RNAP IIin vitro¹³. Identical results were obtained using antibodies thatrecognize RNAP II with unphosphorylated CTD (data not shown). Thus, itappears that the U2AF65 RS moiety localizes the inhibitor totranscription complexes more efficiently than the Tat AD, consistentwith the observations that U2AF65 interacts with RNAP II⁷ and thatfusing an RS domain to a cytoplasmic reporter protein results in nuclearlocalization and interaction with RNAP II^(9,14). The interaction withRNAP II was confirmed by immunofluorescence, in which T-U2AF65-GFP wasseen to co-localize with both unphosphorylated and Ser5P-CTD forms ofpolymerase (FIG. 3 b). Partial co-localization (˜18%) was observed withSC35, a marker of speckle-associated patches⁵. Consistent with thehypothesis that the RS domain drives the interaction with RNAP II,T-RS-GFP showed the same co-localization as the full-length U2AF65T-fusion (data not shown). In addition to interacting with RNAP II,T-U2AF65-GFP also is complexed to P-TEFb (FIG. 3 a), as is the Tat ADfusion without the U2AF65 moiety. The Tat AD K41A mutation, known toabrogate the Tat-cyclin T1 interaction¹², eliminates the interaction ofT-U2AF65-GFP with P-TEFb, supporting the hypothesis that inhibitorpotency results from bivalent interactions involving both the Tat AD andRS domain.

Example 4 Targeting of the Dominant Negative Protein to the HIV Promoter

A primary function of Tat is to enhance transcription elongation³ but italso participates in pre-initiation complex assembly^(3,16). RNaseprotection experiments using promoter proximal (Pp) and distal (Pd)probes indicate that the T-U2AF65 dominant negative primarily inhibitselongation (FIG. 3 c). Tat transfected into HeLa cells substantiallyenhances transcription in the Pd but not Pp region of a luciferasereporter (compare lanes 1 and 2), as previously reported 3, whereas astoichiometric amount of co-transfected T-U2AF65 reduces transcriptionin the Pd region to basal levels but does not effect Pp transcription(lane 3). inhibition is dose responsive (data not shown) and requiresthe U2AF65 moiety as the Tat AD alone shows little inhibition (lane 4).We next used chromatin immunoprecipitation (ChIP) assays to examinerecruitment of RNAP II, Tat, and T-U2AF65 to the HIV promoter and totest the hypothesis that the inhibitor is efficiently localized to thepromoter. To assess complex assembly in an integrated chromatin context,we generated a stable HeLa cell line carrying an LTR-RREIIB-FFLreporter, which was strongly activated by T-Rev (215-fold) and inhibitedby T-U2AF65 in a dose-responsive manner (FIG. 3 d). In the absence ofT-Rev, RNAP II is detected in the Pp but not Pd region (panel 1),implying a block to elongation, while RNAP II is seen in both regionsfollowing T-Rev transfection (panel 2), as previously reported^(16,17).The level of RNAP II detected in the Pp region increases ˜5-fold in thepresence of Tat, consistent with the proposed role of Tat intranscription complex assembly¹⁶. The T-Rev-HA activator was alsodetected in the Pp region (panel 2) but, notably, the T-U2AF65-GFPinhibitor showed even higher occupancy (panel 3); consistent with theobservation that U2AF65 can be detected in the Pp region in the absenceof Tat¹⁷. To more directly evaluate competition between the activatorand inhibitor, we co-transfected both plasmids and observed strongoccupancy of T-U2AF65-GFP in the Pp region whereas no T-Rev-HA could bedetected (panel 4). Furthermore, the Tat AD alone, without the U2AF65moiety, was not detectable at the promoter (panel 5, T-NLS-GFP). Thus,the CHIP experiments support the hypothesis that the T-U2AF65 inhibitoris recruited to the HIV promoter through an interaction with RNAP II,efficiently pre-loading the inhibitor into transcription complexes andblocking entry of the Tat activator.

The specificity of dominant negative inhibition for the HIV promoter isclear (FIG. 1 d), but the co-localization data (FIG. 3 b) suggest that asubstantial amount of RNAP II interacts with the inhibitor, prompting usto test whether T-U2AF65 is recruited to other promoters. Of fivecellular promoters analyzed by ChIP, including the P-TEFb-dependent MHCclass II and hsp70 promoters, only hsp70 showed any detectableT-U2AF65-GFP, unlike the high occupancy observed at the HIV promoter(FIG. 3 e). These data indicate that the efficiency of T-U2AF65recruitment involves interactions other than to RNAP II, likelyincluding interactions with PTEFb and other factors in the transcriptionmachinery.

Example 5 Use of the Tat Dominant Negative to Inhibit HIV Replication

The high potency of the Tat dominant negatives and the requirement ofTat for viral replication suggested that they might be effective HIVinhibitors. To analyze this we generated SupT1 lymphocyte cell linesstably expressing T-U2AF65, T-HIV_(RBD)-U2AF65, or T-BIV_(RBD)-U2AF65dominant negatives or the non-fusion controls, Tat_(AD), Tat,T-BIV_(RBD), or U2AF65, and monitored HIV replication rates usingviruses dependent on either the HIV or BIV Tat-TAR interactions¹⁸. Weobserved striking specificity of the dominant negatives in whichreplication was inhibited only in viruses driven by a non-cognateRNA-protein interaction. Expression of T-U2AF65, which contains no TARRNA-binding domain, markedly suppressed replication of both virusescompared to the Tat_(AD) or U2AF65 controls, with no p24 antigendetectable until 18-20 days after infection (FIGS. 4 a and 4 b).Expression of T-HIV_(RBD)-U2AF65 or T-BIV_(RBD)-U2AF65 inhibitedreplication of the non-cognate virus to a similar extent as T-U2AF65 andshowed only a slight inhibitory effect on the cognate virus (FIGS. 4 aand 4 b). Interestingly, expression of the Tat or T-BIV_(RBD) activatorsactually accelerated replication of the cognate, but not non-cognateviruses, suggesting that Tat levels in these viruses are limiting and/orTat may benefit viral adaptability. In the inhibitor cell lines, virusthat emerged after 18-20 days displayed slow replication kinetics andreached a low plateau of p24 expression that remained constant for atleast 110 days (FIGS. 4 a and 4 b) without producing cytophatic effects.Viral stocks harvested from these cell lines after 30 days displayedidentical growth kinetics as the original stock upon re-infection (FIG.10). Sequencing of integrated viral DNA showed no mutations in the LTRor Tat, indicating that the viruses do not acquire resistance mutationsduring this time period but rather grow poorly under these conditions ofdominant negative inhibitor expression.

Example 6 Tat RBD is Dispensable for Dominant Negative Activity

To assess whether the RBD of Tat contributes to the dominant negativeactivity, we generated U2AF65 fusions to full-length Tat or Tat_(AD) andmeasured their effects using an LTR-BTAR-RL reporter and Tat-BIV_(RBD)activator. Indeed, both T-HIV_(RBD)-U2AF65 and T-U2AF65 inhibitedactivation more than 10-fold at sub-stoichiometric plasmid DNA levelsrelative to the activator (FIG. 5 a). Tat_(AD) without tethered U2AF65,showed little inhibition. Similarly, full-length Tat is a weak dominantnegative inhibitor of BIV Tat-TAR-mediated activation, consistent with aprevious report [1]. In a converse experiment, activation of anLTR-HTAR-FFL reporter by Tat-HIV_(RBD) is potently inhibited by T-U2AF65and T-BIV_(RBD)-U2AF65 but not by un-fused Tat_(AD) or T-BIV_(RBD) (FIG.5 b). Additional control experiments showed that T-HIV_(RBD)-U2AF65 andT-BIV_(RBD)-U2AF65 fusion proteins activated expression of their cognatereporters to about 50% of the un-fused protein levels and thatexpression of non-Tat fused U2AF65 did not inhibit activation (data notshown).

Example 7 Relative Expression Levels of Tat Activator and DominantNegative

Immunofluorescence experiments showed that the T-Rev activator andT-U2AF65 dominant negative were expressed similarly and localized to thenucleus (FIG. 2 a). We analyzed protein levels more quantitatively byWestern blot using HA-tagged proteins and confirmed that stoichiometricplasmid levels express similar amounts of protein (FIG. 6). Thus, thehigh potency of T-U2AF65 is striking given that the best reporteddominant negative Tat inhibitors require more than 5-fold higherinhibitor levels to reduce activation by less than 10-fold [2-4].

Example 8 Inhibition Activities of Other T-Fusions

The potent inhibition observed with T-SF1 and T-U2AF65 prompted us toevaluate whether fusions to other transcription or RNA processingfactors might also act as dominant negatives. While T-SF1 was slightlyless potent than T-U2AF65, a fusion to the SR-protein 9G8 (T-9G8) wasnearly as potent as T-U2AF65 (FIG. 7). Fusions to the CstF1polyadenylation factor known to be recruited to the CTD[5,6] and to anhnRNP A1 fusion containing RRM RBDs also showed some modest inhibition(about 4 fold). In contrast, fusions to the DNA-binding transcriptionfactors Sp1 or Re1A showed relatively little inhibition (about 2 fold),consistent with a previous report showing little inhibitory effect byfusing Tat to other DNA-binding factors [7]. T-TAF8 also showed noinhibition, consistent with the proposal that Tat- activation is exertedthrough a TFIID-containing TBP complex but independent of TBP-associatedfactors (TAFs) [8]. All T-fusions were nuclear and expressed at similarlevels as judged by indirect immunofluorescence (FIG. 7), except thatT-Re1A showed more prominent perinuclear localization in the absence ofTNF-α activation. Thus, T-fusions to splicing factors containing RSdomains (T-U2AF65 and T-9G8) are the most potent inhibitors.

Example 9 Possible Contribution of Subnuclear Localization to DominantNegative Activity

Deleting the RS domain of T-U2AF65 eliminates dominant negative activity(see T-U2AF65AΔS in FIG. 2 b) and its subcellular localization isstrikingly different (FIG. 2 b). While T-U2AF65 shows speckle-associatedpatches typical of splicing factors, U2AF65ΔRS is spread throughout thenucleoplasm. To evaluate whether the Tat or U2AF65 moieties wereresponsible for these localization patterns, we first comparedlocalization of T-U2AF65-GFP, U2FA65-GFP, and the inactiveT(K41A)-U2AF65-GFP variant (FIG. 8). All three are localized similarlyin speckles (Spk), implying that U2AF65 drives the localization of thedominant negative and that localization is necessary but not sufficientfor inhibition.

An even more striking subnuclear localization pattern is seen forT-RS-GFP bearing only the U2AF65 RS-domain in which only a few (10-30)bright clusters are observed (FIG. 8). Again, the Tat AD K41A mutationdoes not alter its localization. Interestingly, an RS-GFP fusion lackingthe Tat AD is no longer localized to speckles but rather to nucleoli(FIG. 8), suggesting that both the AD and RS domains of T-RS contributeto its speckle localization in this shorter context. Deletion of theRS-domain in both U2AF65 and T-U2AF65 also eliminates localization tospeckles and shows a nuclear pattern with nucleolar exclusion (FIG. 8),further highlighting the importance of the RS domain for specklelocalization.

Example 10 Dominant Negative Expression Levels and Functional Activityin Stable SupT1 Populations

To assess expression levels of the Tat activators (Tat, Tat_(AD) andT-BIV_(RBD)) and dominant negative inhibitors (T-U2AF65,T-HIV_(RBD)-U2AF65, and T-BIV_(RBD)-U2AF65) in the stable SupT 1populations used for the viral replication assays, we first determinedmRNA steady-state levels for each protein by quantitative real-timeRT-PCR, using two sets of primers that amplify Tat or U2AF65 portions ofthe mRNAs. While the RNA expression levels varied widely betweensamples, all were clearly detectable, with the SupT1-Tat populationexpressing the highest levels (normalized expression level of 370units), followed by T-BIV_(RBD) (120 units), Tat_(AD) (100 units),Tat_(AD)-U2AF65 and T-BIV_(RBD)-U2AF65 (35 units), and Tat-U2AF65 (7units). We next characterized expression in a more functional assay invivo by transfecting each stable cell population with an activatable GFPreporter, depending on the Tat protein expressed, and monitored activityby flow cytometry (data not shown). All stable SupT1 populationsexpressing the full-length Tat moiety activated an LTR-HTAR-GFPreporter, varying from 9-20 fold, while cell lines expressing Tat_(AD)did not activate. Stable cell populations expressing T-BIV_(RBD)activated an LTR-BTAR-GFP reporter about 7-9 fold but not anLTR-HTAR-GFP reporter. The Tat_(AD)-U2AF65-expressing population weaklyactivated an LTR-BPS-GFP reporter, through its polypyrimidine tract(PPT) binding site [9]. This weak activity likely reflected thegenerally lower activation observed with the U2AF65-PPT interaction [9]and, probably, the low transfection efficiency of the SupT1 cells. Thus,expression of each Tat or Tat-fusion protein could be confirmed byRT-PCR and functional assays, but expression levels generally appearedlow, as expected for a stable cell population transduced by a retrovirusbut not clonally selected [10]. Weak expression was further confirmed byWestern blot and immunofluorescence analysis using an anti-Tat antibodywhere expression was virtually undetectable (data not shown).

We also estimated the activities of the integrated dominant negatives inthe SupT1 cell lines using functional assays. Cells were co-transfectedwith a fixed amount of the LTR-HTAR-FFL or LTR-BTAR-FFL reporter andvarying concentrations of the corresponding Tat activator and levels ofinhibition were measured. For example, SupT1 cells expressing T-U2AF65and T-BIV_(RBD)-U2AF65 were co-transfected with the LTR-HTAR-FFLreporter and HIV Tat, and no significant activation was observed at lowlevels (0.1-1 ng) of transfected activator (FIG. 9 a). Significantactivation was observed with higher (5-20 ng) plasmid amounts, furtherconfirming that the cell lines do not express very large amount ofprotein and consequently do not block Tat activity completely. It seemsprobable that more highly expressing dominant negative cell lines can beidentified through cloning that would result in even more effectiveviral inhibition than observed (FIG. 4).

Example 11 Lack of Dominant Negative Activity on Cellular Promoters

Transcriptional squelching has been described for many dominant negativetranscription factors, such as yeast Gal4, and herpes simplex virusVP16, where common components of the transcriptional apparatus become“titrated of” of promoters [11,12]. Typically, these dominant negativesare rather promiscuous because the target co-activators do not need tobe bound to the specific promoter. For HIV Tat, for example, it has beenshown that Tat over-expression leads to decreased transcription from anMHC class II promoter, because both Tat and the class II transactivator(CIITA) require P-TEFb to function [13]. Because the Tat dominantnegatives described here apparently operate via co-transcriptionalrecruitment to the HIV promoter, we suspected that they might displaypromoter specificity, unlike the more traditional dominant negatives.Reporter experiments show that T-U2AF65 has specificity for the HIVpromoter versus other P-TEFb-regulated promoters (FIG. 1). To furtheranalyze promoter specificity, we compared the relative expression levelsof nine endogenous transcripts in the SupT1-Tat_(AD) (non-inhibitor)-and SupT1-T-U2AF65 (inhibitor)-expressing stable cell lines usingquantitative RT-PCR and observed no significant differences in RNAlevels from any of these promoters (FIG. 9 b). The tested genes encodehousekeeping proteins (actin, GAPDH, HPRT1), regulatory factors (TBP,hnRNPA1, EEF1G), and include an MHC class II (HLA-DQA1) and two otherP-TEFb regulated genes (IL-8 and AR) [14]. Thus, whereas expression ofT-U2AF65 effectively blocks Tat activation and HIV replication, it showsno significant effect on cellular promoters.

Example 12 Virus Emerging from the Dominant-Negative-InducedLatency-Like State Behaves as the Original Stock

We observed that virus eventually emerged after 18-20 days in theinhibitor-containing cell lines but with low replication kinetics andreaching a low steady-state plateau of p24 expression (FIG. 4). Nomutations were found in these emergent viruses in the LTR or Tat codingregion (data not shown), suggesting the cellular expression of thedominant negative inhibitor continuously suppressed replication. To testthis, we harvested viruses that emerged after 30 days and performed are-infection experiment to compare the kinetics of the original andemergent viruses. Indeed, identical growth kinetics were observed whenthe initial or new viral stocks were used to infect the SupT1-T-U2AF65inhibitor cell line, reaching the same chronic p24-expressing plateau,whereas rapid growth was observed for both stocks in the SupT1-Tat_(AD)control cells (FIG. 10). As expected, inhibitor-expressing cellsinfected at a high m.o.i. (10 versus 1) showed a cytopathic effect,although again slower replication kinetics was observed than in thecontrol cells (data not shown). Thus, even with low inhibitor expressionand a high m.o.i. some protective effect still is seen, highlighting theefficacy of the inhibitor and the balance between activator andinhibitor observed upon transfection of the SupT1 cell lines (FIG. 9 a).

Conclusions

The potent Tat dominant negative inhibitors described in this workrepresent a new mechanistic class in which we hypothesize that atranscription factor AD is efficiently recruited to its promoter via atethering signal, in this case an RS domain, among other specificcontacts with the transcriptional apparatus. Unlike other dominantnegatives, these Tat inhibitors function at stoichiometric or evensub-stoichiometric levels and do not require the considerableover-expression typically required for squelching or other simplecompetition mechanisms^(1,19). We speculate that their specificity andpotency is imposed by localization, first at the sub-cellular andsub-nuclear levels and second by efficient recruitment to the promoter.Ptashne and Gann proposed the concept of “regulated localization”, wherespecificity typically is imposed by simple binding interactions betweena locator, the transcriptional machinery, and the DNA²⁰. We propose thatcombining localization functions within a single polypeptide cansubstantially enhance activity. In the case of the T-U2AF65 inhibitor,it appears that the Tat AD provides the dominant negative function, inpart through interactions with P-TEFb at the HIV promoter, while the RSdomain provides additional localization and timing functions utilizingco-transcriptional mechanisms that RNA-processing factors, including SRproteins, use to load into transcription complexes^(10,11). Thishypothesis is supported by the observations that RS-domain-containingproteins localize to sub-nuclear speckles, which are thought to anchorsplicing factors to the nuclear matrix and facilitate assembly with RNAPII,²¹ and that Tat and P-TEFb co-localize to nuclear speckles²². Itremains to be determined if other transcription factors, including thosethat do not function at the elongation step, can be efficientlylocalized and assembled into transcription complexes in a similarmanner, and if other types of targeting domains may be used.

HIV replication is substantially inhibited by low-level expression ofthe dominant negative in stable cell lines (FIG. 4), even withoutoptimizing and selecting for lines with high activity (FIG. 9). It isinteresting that these cells establish a chronic infection withoutcytopathic effects, reminiscent of other cellular environments that mayresemble latent stages of HIV infection²³. The balance of Tat clearlyaffects viral replication rates²⁴ and also can drive phenotypicdiversity²⁵, and here we show that expression of the dominant negativeprovides another means to alter the Tat balance. Other dominant negativeHIV proteins have been used to suppress HIV replication, including thenuclear export-deficient Rev M10 mutant²⁶, but resistance mutations havebeen found²⁷ and relatively high expression levels are required forinhibition despite the oligomeric nature of Rev^(27,28). It will beinteresting to examine mechanisms by which resistance to the Tatdominant negative might arise and to evaluate its therapeutic potential.

Methods and Materials

Transcriptional Activation and Inhibition Reporter Assays

HeLa cells were transfected with GFP or firefly luciferase (FFL)reporter plasmids (typically 25 ng), appropriate amounts of Tatactivator and inhibitor plasmids, and 5 ng of a CMV-Renilla luciferase(RL) plasmid using the Polyfect lipid transfection reagent (Qiagen) in a48-well format. Reporter activity was measured 48 hr post-transfectionusing a Becton-Dickinson FACS Calibur (FIG. 1 a) or Dual-Glo luciferaseassay (Promega). All LTR reporter plasmids used contained an internalribosome entry site (IRES) upstream of the FFL gene to ensure efficienttranslation irrespective of the 5′UTR sequence used, and RL activity wasused to normalize for transfection efficiencies. For experimentspresented in FIG. 2, cells were transfected with 10 ng of activator and2.5 or 10 ng of Tat-fusion plasmids. All activation assays wereperformed in triplicate, and error bars represent the SD of the mean.

Microsopy

HeLa or stably-integrated HeLa LTR-RREIIB-FFL cels were grown to 50%confluence on glass cover slips, transfected with 100 ng of plasmidDNAs, fixed in 4% paraformaldehyde in 1×PBS buffer (pH 7.6) 24 hrpost-transfection, rinsed twice with PBS, and permeabilized withPBS-Triton 0.5% for 10 min at 4° C. Nonspecific antibody sites wereblocked in 1×PBS, 3% goat serum, and 4% BSA for 1 hr at roomtemperature, cells were incubated with primary antibodies for 1 hr atroom temperature, washed three times with PBS, incubated withappropriate Alexa 488- or Alexa 546-coupled secondary antibodies(Molecular Probes) for 1 hr at room temperature, and washed three timeswith PBS. Cells were mounted on DAPI-containing Vecta-shield slides(Vector Labs). Light microscopy was done using an LSM510 confocalmicroscope (Zeiss) and images were processed using LSM (Zeiss) software.

Co-Immunoprecipitation

To examine association of dominant negative inhibitors with RNAP II,HeLa cells were transiently transfected with T-U2AF65-GFP,T(K41A)-U2AF65-GFP, or T-NLS-GFP, and nuclear extracts were preparedwith RIPA buffer. Half of the extract was used directly for theimmunoprecipitation and the remaining half was treated with 1 μg ofRNAse A, which was sufficient to quantitatively digest the RNA from 10⁶HeLa cells. RNAP II was immunoprecipitated using agarose-conjugated to8WG16 and H14 antibodies overnight at 4° C. with mild shaking.Similarly, GFP-tagged proteins were immunoprecipitated usingagarose-conjugated GFP-antibodies. After centrifuging and washing thebeads immunocomplexes were dissociated by boiling for 10 min in 2×gelloading buffer, samples were separated by 10% SDSPAGE, transfered toPVDF, and analyzed by Western blot.

RNase Protection Assay

HeLa cells were transfected with the pLTR-HTAR-FFL reporter alone orwith activator and inhibitor-expressing plasmids, total RNA wasextracted using TRIzol (Invitrogen), and 15 μg of each sample washybridized with proximal and distal probes corresponding to HIV promoterand luciferase ORF regions, respectively. The antisense probes weresynthesized using a T3/T7 MaxiScript kit (Ambion) from plasmid templateslinearized at a KpnI site, hybridization was performed withapproximately 10,000 cpm of ³²P-CTP-labeled probe (in 80% formamide, 40mM PIPES, 400 mM NaCl, 1 mM EDTA) incubated at 42° C. overnight, RNasedigestion was performed for 1.5 hr at 30° C. (in 10 mM Tris pH 8.0, 300mM NaCl, 5 mM EDTA, 11 units/ml of RNase A, 11 units/ml RNase T1),samples were treated with proteinase K, extracted withphenol/chloroform, and RNA duplexes were precipitated with ethanol andglycogen carrier. RNAs were separated on a 6% polyacrylamide/8 M ureagel and visualized and quantified using a Typhoon phosphorimager(Molecular Dynamics). Experiments were performed in duplicate, witherrors bars representing the SD of the mean.

Selection of a HeLA LTR-RREIIB-FFL Reporter Cell Line and ChIP Assays

HeLa cells were transfected in 6-well plates with a pcDNA3.1-derivedplasmid (Invitrogen) bearing the LTR-RREIIB-FFL using Polyfect reagent(Qiagen). Clones were selected over more than four weeks in D-MEM-10%FBS supplemented with 750 μg/ml of G418 (Gibco). Twenty clones wereanalyzed for activation by pSV-T-Rev-HA by luciferase assays and asingle highly active clone was chosen for ChIP analyses. ChIP assayswere performed as described²⁹ with minor modifications. HeLaLTR-RREIIB-FFL reporter cells were transfected with various expressorplasmids (5 μg each) using 30 μl of Lipofectamine 2000 (Invitrogen) per25 cm culture dish, incubated for 36 hr, and washed in PBS. Chromatinwas cross-linked with 1% formaldehyde for 15 min at RT and the reactionstopped by adding glycine to 125 mM. Cells were washed with PBS andharvested in RIPA buffer, and samples were sonicated to generate DNAfragments<500 bp. For immuno-precipitations, 1 mg of protein extract waspre-cleared for 2 hr with 40 μl of a 50% slurry of 50:50 proteinA/G-agarose and -then incubated with protein A/G-agarose and theappropriate antibodies overnight at 4° C. preblocked with 1 mg/ml and0.3 mg/ml of salmon sperm DNA. Immunocomplexes were recovered usinganti-rabbit IgG/protein A/G-agarose beads (Santa Cruz), beads werewashed twice with RIPA bufer, four times with ChIP wash buffer (100 mMTris-HCl, pH 8.5, 500 mM LiCL, 1% v/v Nonidet P-40, 1% w/v deoxycholicacid), twice with RIPA buffer, and twice with 1×TE buffer.Immunocomplexes were eluted in 1% SDS for 10 min at 65° C. andcross-linking was reversed by adjusting to 200 mM NaCl and incubatingfor 5 hr at 65° C. A fraction of purified DNA was used for PCRamplification, with 25-32 cycles performed in the exponential rangedepending on the particular primers and antibodies. To ensure linearity,control PCR reactions were performed for one cycle using twice and halfthe amount of sample. PCR products (100-250 bp) were quantified byincorporation of SyBr Green and fluorescence detection (MJ Research) andby visualization on 2% agarose gels stained with ethidium bromide, usingPCR products from known input DNAs as standards and IQMac1.2 foranalysis. Primer sequences are provided in Supplementary Information.

Dominant Negative-Expressing SupT1 Cells and Viral Replication Kinetics

Plasmids expressing Tat_(AD), Tat, T-BIV_(RBD), T-U2AF65,T-HIV_(RBD)-U²AF65, T-BIV_(RBD)-U²AF⁶5, and U2AF65 were constructed in apBMN retroviral vector (kindly provided by G. Nolan), using an SV40promoter to express the Tat or Tat-fusion proteins. Plasmids weretransfected into ONX packaging cells using the Polyfect reagent, and theretrovirus-containing supernatant recovered after 48 hr was used totransduce human CD4+ SupT1 cells. Populations of stable integrants wereselected by growing cells in 2 mg/ml G418 (Invitrogen) for at least 4weeks. Relative expression levels for each protein were assessed byreal-time RT-PCR, transcriptional activation of transfected reporterplasmids and Western blotting (Supplementary Information). Each stableSupT1 population was infected with an HIV Tat-TAR-dependent (R7HTat/HTAR) or BIV Tat-TAR-dependent (R7 HBTat/BTAR) virus¹⁸at an m.o.iof 1. Supernatant samples were harvested at different intervalsfollowing infection and the amount of viral replication was monitored byp24 antigen expression using ELISA (Immuno Diagnostics, Inc.) over aperiod of 110 days. Each experiment was performed in duplicate and meanvalues of p24 were calculated.

RNA Isolation and Expression Levels by Quantitative Real-Time RT-PCR

Total RNA was isolated from cells using the Trizol reagent according tomanufacturer instructions (Invitrogen). Randomly primed cDNA wasprepared from 1 μg of total RNA using MMULV reverse transcriptase (NewEngland Biolabs). One twentieth of the resultant cDNA was amplified in35 μl reactions containing 1.25 units of Taq DNA polymerase (ABI), 1.5mM MgCl₂, 300 nM of each primer, 0.5 mM dNTP mix, and 0.2X SYBR green Idye (Molecular Probes) in 1×Taq polymerase buffer. Real-time PCR wasperformed in an Opticon 2 DNA Engine (MJ Research) and analyzed usingthe Ct method (Applied Biosystems Prism 7700).

Expression Analysis by Western Blot

To more quantitatively assess relative inhibitor and activatorexpression levels, HeLa cells were co-transfected with 300 ng of pEGFPN3(Clontech) and either 1.35 μg of pSV2-T-Rev-HA, 1.35 μgpSV2-T-U2AF65-HA, or both plasmids in 6-well plates. Nuclear extractswere prepared using NE-PER reagents (Pierce), samples were separated ona 12.5% SDS-PAGE gel, transferred to nitrocellulose, and probed withanti-HA, anti-GFP, or anti-nucleolin antibodies.

Functional Analysis of Protein Expression and Activity in SupT1 CellLines

Stable SupT1 G418-resistant cell populations (3×10⁶ cells) weretransfected by electroporation (Bio-Rad, 250V, 0.975 μF) withLTR-HTAR-GFP or LTR-BPS-BTAR-GFP reporters to assess the activities ofintegrated plasmids expressing Tat or T-fusion proteins. After 48 hours,cells were analyzed by flow cytometry and GFP activity was quantitatedusing Celquest software (Becton Dickinson). Populations expressing Tatand derivatives were transfected with LTR-HTAR-GFP, populationsexpressing T-BIV_(RBD) and derivatives were transfected withLTR-BPS-BTAR-GFP, and populations expressing U2AF65 fusions weretransfected with LTR-BPS-BTAR-GFP, which contains a BPS and PPT thatbinds U2AF65 cooperatively with SF1 [9]. For luciferase assays, we usedthe LTR-HTAR-FFL or LTR-BTAR-FFL reporters and CMV-RL as an internalcontrol for data normalization.

Genomic DNA xtraction from SupT1-Infected Cells and Viral GenomeSequencing

SupT1-T-U2AF65, SupT1-T-BIV_(RBD)-U2AF65, and SupT1-T-HIV_(RBD)-U2AF65infected populations (about 1×10⁶ cells) were harvested 25 dayspost-infection and genomic DNA was extracted using Flexigene accordingto manufacturer instructions (Qiagen). DNA was amplified by PCR usingTurbo Pfu (Stratagene), with primer pair specific to regions of the HIVLTR promoter and surrounding Tat coding sequence. PCR-amplified DNA wasgel purified (Qiagen) and cloned into a TOPO vector (Invitrogen). Eightclones from each cell population were sequenced, and sequences werecompared to the original viral isolate, HXB2, using the NCBI BLASTalgorithm.

SUPPLEMENTARY REFERENCES

-   1. Carol, R. et al., J Virol, 66:2000-7 (1992).-   2. Gren, M. et al., Cell, 58:215-23 (1989).-   3. Pearson, L. et al., Proc Natl Acad Sci USA, 87:5079-83 (1990).-   4. Caputo, A. et al., Gene Ther, 3:235-45 (1996).-   5. McCracken, S. et al., Nature, 385:357-61 (1997).-   6. Fong, N. & Bentley, D. L., Gene Dev, 15:1783-95 (2001).-   7. Fraisier, C. et al., Gene Ther 5:946-54 (1998).-   8. Raha, T. et al., PLoS Biol, 3:e44 (2005).-   9. Peled-Zehavi et al., Mol Cell Biol, 21:5232-41 (2001).-   10. Hamm, T. E. et al., J Virol, 73:5741-7 (1999).-   11. Hope, I. A. & Struhl, K., Cell, 46:885-94 (1986).-   12. Friedman, A. et al., Nature, 335:452-4 (1988).-   13. Kanazawa, S. et al., Immunity, 12:61-70 (2000).

14. Luecke, H. F. & Yamamoto, K. R., Gene Dev, 19:1116-27 (2005). TABLE1 Nuclear localized proteins Last updated: 2006-02-26 nucleus Accession:GO:0005634 Ontology: cellular_component Synonyms: None Definition: Amembrane-bounded organelle of eukaryotic cells in which chromosomes arehoused and replicated. In most cells, the nucleus contains all of thecell's chromosomes except the organellar chromosomes, and is the site ofRNA synthesis and processing. In some species, or in specialized celltypes, RNA metabolism or DNA replication may be absent. Comment: NoneTerm Lineage Graphical View all: all (<167657) GO:0005575:cellular_component (<105038) GO:0005623: cell (<75863) GO:0005622:intracellular (<61387) GO:0043229: intracellular organelle (<55495)GO:0043231: intracellular membrane-bound organelle (<51579) GO:0005634:nucleus (<10723) GO:0005634: nucleus (<10723) GO:0043226: organelle(<55511) GO:0043229: intracellular organelle (<55495) GO:0043231:intracellular membrane-bound organelle (<51579) GO:0005634: nucleus(<10723) GO:0043227: membrane-bound organelle (<51596) GO:0043231:intracellular membrane-bound organelle (<51579) GO:0005634: nucleus(<10723) External References InterPro (333) MIPS_funcat (1) Pfam (221)PRINTS (94) ProDom (25) PROSITE (99) SMART (46) SP_KW (1) TIGR_role (1)All Gene Product Associations (1790 results) Get ALL associations here:Direct Associations All Associations All Associations With Terms FilterAssociations DatasourceAllFlyBaseSGDMGIgenedb_spombeUniProtTAIRdictyBaseWorm-baseEnsemblRGDTIGR_CMRTIGRFAMSTIGR_Ath1TIGR_Tba1Gramenegenedb_tsetsegenedb_tbruceigenedb_pfalciparumgenedb_lmajorZFINEvidence Code All Curator ApprovedICIMPIGIIPIISSIDAIEPTASNAS Species AllA. japonica A. niger A. platyrhynchos A. thaliana A. trivirgatus B.anthracis str. Am B. coronavirus B. indicus B. mori B. taurus C.aethiops C. albicans C. briggsae C. burnetii RSA 493 C. carpio C.elegans C. familiaris C. griseus C. jacchus C. jejuni RM1221 C.porcellus C. torquatus atys D. discoideum D. erecta D. ethenogenes 195D. mauritiana D. melanogaster D. pseudoobscura D. rerio D. sechellia D.simulans D. sp. D. virilis D. yakuba E. caballus F. catus G. gallus G.gorilla G. gorilla gorilla G. sulfurreducens PCH. lar H. sapiens L.major L. monocytogenes str M. auratus M. capsulatus str. B M.fascicularis M. fuscata fuscata M. monax M. mulatta M. musculus M.musculus castaneu M. musculus domestic M. musculus molossin M. musculusmusculus M. natalensis M. nemestrina M. parviflora M. unguiculatus O.aries O. cuniculus O. kitabensis O. longistaminata O. mykiss O. nivaraO. officinalis O. sativa O. sativa (indica cu O. sativa (japonica O.vulgaris P. anubis P. falciparum P. monodon P. pygmaeus P. sativum P.syringae pv. toma P. syringae pv. toma P. troglodytes Panicum R.norvegicus R. sp. S. cerevisiae S. coronavirus S. oedipus S. oneidensisS. oneidensis MR-1 S. pombe S. pomeroyi DSS-3 S. sciureus S. scrofa S.sp. PCC 6803 T. brucei T. brucei TREU927 T. cambridgei T. vulpecula V.arvensis V. cholerae O1 biova V. odorata X. laevis X. tropicalis

Symbol Qualifier Sequence/GOst Information Source Evidence Reference2A5D HUMAN Splice Isoform Delta-1 of UniProt TAS PMID: 8703017Serine/threonine protein phosphatase 2A, 56 kDa regulatory subunit,delta isoform, protein from Homo sapiens 2A5G HUMAN Splice IsoformGamma-3 UniProt IDA PMID: 8703017 of Serine/threonine Proteinphosphatase 2A, 56 kDa regulatory subunit, gamma isoform, protein fromHomo sapiens 2AAA HUMAN Serine/threonine protein UniProt NAS PMID:11007961 phosphatase 2A, 65 kDa regulatory subunit A, alpha isoform,protein from Homo sapiens 2AAB HUMAN Serine/threonine protein UniProtISS UniProt: P30154 phosphatase 2A, 65 kDa regulatory subunit A, betaisoform, protein from Homo sapiens 2ACC HUMAN Protein phosphatase 2,UniProt TAS PMID: 10629059 regulatory subunit B″, isoform 1, proteinfrom Homo sapiens 4ET HUMAN Splice Isoform 1 of UniProt TAS PMID:10856257 Eukaryotic translation initiation factor 4E transporter,protein from Homo sapiens AATF HUMAN Protein AATF, protein UniProt IDAPMID: 12429849 from Homo sapiens AB2BP HUMAN Splice Isoform 1 of UniProtNAS PMID: 10833507 Amyloid beta A4 protein- binding family A member2-binding protein, protein from Homo sapiens ABCCD HUMAN Splice Isoform1 of UniProt NAS UniProt: Q9NSE7 Putative ATP-binding cassettetransporter C13, protein from Homo sapiens ABL1 HUMAN Splice Isoform IAof UniProt NAS PMID: 8242749 Proto-oncogene tyrosine- protein kinaseABL1, protein from Homo sapiens ACINU HUMAN Splice Isoform 1 of UniProtIDA PMID: 10490026 Apoptotic chromatin condensation inducer in thenucleus, protein from Homo sapiens ACL6B HUMAN Actin-like protein 6B,UniProt IDA PMID: 10380635 protein from Homo sapiens ACTN4 HUMANAlpha-actinin 4, protein UniProt TAS PMID: 9508771 from Homo sapiensADA10 HUMAN ADAM 10 precursor, UniProt ISS UniProt: O14672 protein fromHomo sapiens ADA2 HUMAN Transcriptional adapter 2- UniProt TAS PMID:8552087 like, protein from Homo sapiens AF9 HUMAN Protein AF-9, proteinUniProt TAS PMID: 8506309 from Homo sapiens AFF3 HUMAN AF4/FMR2 familyUniProt TAS PMID: 8555498 member 3, protein from Homo sapiens AHNK HUMANNeuroblast differentiation- UniProt NAS PMID: 1608957 associated proteinAHNAK, protein from Homo sapiens AHR HUMAN Aryl hydrocarbon receptorUniProt IDA PMID: 10395741 precursor, protein from Homo sapiens AIF1HUMAN Allograft inflammatory UniProt TAS PMID: 9614071 factor 1, proteinfrom Homo sapiens AIPL1 HUMAN Aryl-hydrocarbon- UniProt IDA PMID:12374762 interacting protein-like 1, protein from Homo sapiens AIREHUMAN Splice Isoform 1 of UniProt NAS PMID: 9398840 Autoimmuneregulator, protein from Homo sapiens AKAP8 HUMAN A-kinase anchor proteinUniProt TAS PMID: 9473338 8, protein from Homo sapiens AKIP HUMAN Aurorakinase A- UniProt IDA PMID: 12244051 interacting protein, protein fromHomo sapiens AKP8L HUMAN A-kinase anchor protein- UniProt TAS PMID:10761695 like protein 8, protein from Homo sapiens ALP HUMANN-acetyltransferase-like UniProt NAS PMID: 11214970 protein, proteinfrom Homo sapiens ALX4 HUMAN Homeobox protein UniProt NAS PMID: 11137991aristaless-like 4, protein from Homo sapiens AN32A HUMAN Acidicleucine-rich UniProt IDA PMID: 11555662 nuclear phosphoprotein 32 familymember A, protein from Homo sapiens AN32E HUMAN Acidic leucine-richUniProt ISS UniProt: Q9BTT0 nuclear phosphoprotein 32 family member E,protein from Homo sapiens ANDR HUMAN Androgen receptor, UniProt IDAPMID: 15572661 protein from Homo sapiens ANKR2 HUMAN Splice Isoform 1 ofUniProt ISS PMID: 1204005 Ankyrin repeat domain protein 2, protein fromHomo sapiens ANM1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 10749851Protein arginine N- methyltransferase 1, protein from Homo sapiens ANM2HUMAN Protein arginine N- UniProt TAS PMID: 9545638 methyltransferase 2,protein from Homo sapiens AP2A HUMAN OTTHUMP00000016011, UniProt TASPMID: 8321221 protein from Homo sapiens APBB1 HUMAN Splice Isoform 1 ofUniProt ISS UniProt: O00213 Amyloid beta A4 precursor protein-bindingfamily B member 1, protein from Homo sapiens ISS UniProt: Q96A93 APBB2HUMAN Splice Isoform 1 of UniProt ISS UniProt: Q92870 Amyloid beta A4precursor protein-binding family B member 2, protein from Homo sapiensAPBP2 HUMAN Amyloid protein-binding UniProt NAS PMID: 11742091 protein2, protein from Homo sapiens APC HUMAN Splice Isoform Long of UniProtIDA PMID: 12072559 Adenomatous polyposis coli protein, protein from Homosapiens APEG1 HUMAN Hypothetical protein UniProt TAS PMID: 8663449FLJ46856, protein from Homo sapiens APEX1 HUMAN DNA-(apurinic or UniProtIDA PMID: 9119221 apyrimidinic site) lyase, protein from Homo sapiensAPLP2 HUMAN Splice Isoform 1 of UniProt IDA PMID: 7702756 Amyloid-likeprotein 2 precursor, protein from Homo sapiens ARD1H HUMAN N-terminalUniProt IDA PMID: 15496142 acetyltransferase complex ARD1 subunithomolog, protein from Homo sapiens ARI1A HUMAN Splice Isoform 1 of AT-UniProt NAS UniProt: O14497 rich interactive domain- containing protein1A, protein from Homo sapiens ARI2 HUMAN Ariadne-2 protein UniProt TASPMID: 10422847 homolog, protein from Homo sapiens ARI3A HUMAN AT-richinteractive UniProt NAS UniProt: Q99856 domain-containing protein 3A,protein from Homo sapiens ARI4A HUMAN Splice Isoform I of AT- UniProtTAS PMID: 8414517 rich interactive domain- containing protein 4A,protein from Homo sapiens IDA PMID: 11283269 ARI5B HUMAN Splice Isoform1 of AT- UniProt IC PMID: 15640446 rich interactive domain- containingprotein 5B, protein from Homo sapiens ARL4A HUMAN ADP-ribosylationfactor- UniProt TAS PMID: 10462049 like protein 4A, protein from Homosapiens ARL4C HUMAN ADP ribosylation factor- UniProt TAS PMID: 10462049like protein 7, protein from Homo sapiens ARNT2 HUMAN Aryl hydrocarbonreceptor UniProt IDA PMID: 12239177 nuclear translocator 2, protein fromHomo sapiens ARNT HUMAN Splice Isoform Long of UniProt TAS PMID: 1317062Aryl hydrocarbon receptor nuclear translocator, protein from Homosapiens ASCL2 HUMAN Achaete-scute homolog UniProt NAS PMID: 8751384 2,protein from Homo sapiens ASH2L HUMAN Splice Isoform 1 of UniProt IDAPMID: 15199122 Set1/Asb2 histone methyltransferase complex subunit ASH2,protein from Homo sapiens ASPP1 HUMAN Apoptosis stimulating of UniProtIDA PMID: 11684014 p53 protein 1, protein from Homo sapiens ATBF1 HUMANSplice Isoform A of UniProt TAS PMID: 1719379 Alpha-fetoprotein enhancerbinding protein, protein from Homo sapiens ATE1 HUMAN Splice IsoformATE1-1 of UniProt IDA PMID: 9858543 Arginyl-tRNA--protein transferase 1,protein from Homo sapiens ATF4 HUMAN Cyclic AMP-dependent UniProt ISSUniProt: P18848 transcription factor ATF- 4, protein from Homo sapiensATF6B HUMAN Splice Isoform 1 of Cyclic UniProt TAS PMID: 8586413AMP-dependent transcription factor ATF-6 beta, protein from Homo sapiensATN1 HUMAN Atropbin-1, protein from UniProt TAS PMID: 10814707 Homosapiens ATRX HUMAN Splice Isoform 4 of UniProt TAS PMID: 7874112Transcriptional regulator ATRX, protein from Homo sapiens ATX1 HUMANAtaxin-1, protein from UniProt TAS PMID: 7647801 Homo sapiens ATX2 HUMANAtAxin 2, protein from UniProt TAS PMID: 10973246 Homo sapiens ATX7HUMAN Splice Isoform a of UniProt TAS PMID: 10441328 Ataxin-7, proteinfrom Homo sapiens AURKC HUMAN Splice Isoform 1 of UniProt TAS PMID:10066797 Serine/threonine-protein kinase 13, protein from Homo sapiensAXN1 HUMAN Axin 1, protein from UniProt IDA PMID: 12072559 Homo sapiensAXN2 HUMAN Axin-2, protein from UniProt IDA PMID: 12072559 Homo sapiensBAP1 HUMAN Ubiquitin carboxyl- UniProt TAS PMID: 9528852 terminalhydrolase BAP1, protein from Homo sapiens BARD1 HUMAN BRCA1-associatedRING UniProt IMP PMID: 15632137 domain protein 1, protein from Homosapiens IDA PMID: 15265711 BAZ1B HUMAN Splice Isoform 1 of UniProt NASPMID: 11124022 Bromodomain adjacent to zinc finger domain protein 1B,protein from Homo sapiens BC11A HUMAN Splice Isoform 1 of B-cell UniProtNAS UniProt: Q9H165 lymphoma/leukemia 11A, protein from Homo sapiensBCL6 HUMAN B-cell lymphoma 6 UniProt IDA PMID: 10898795 protein, proteinfrom Homo sapiens BCLF1 HUMAN Splice Isoform 1 of Bcl-2- UniProt NASUniProt: Q9NYF8 associated transcription factor 1, protein from Homosapiens BCOR HUMAN Splice Isoform 1 of BCoR UniProt IDA PMID: 10898795protein, protein from Homo sapiens BHLH2 HUMAN Class B basic helix-loop-UniProt NAS PMID: 9240428 helix protein 2, protein from Homo sapiensBHLH3 HUMAN Class B basic helix-loop- UniProt NAS UniProt: Q9C0J9 helixprotein 3, protein from Homo sapiens BI1 HUMAN Bax inhibitor-1, proteinUniProt TAS PMID: 8530040 from Homo sapiens BINCA HUMAN Splice Isoform 1of UniProt NAS PMID: 15637807 Bcl10-interacting CARD protein, proteinfrom Homo sapiens BLMH HUMAN Bleomycin hydrolase, UniProt TAS PMID:8639621 protein from Homo sapiens BNC1 HUMAN Zinc finger protein UniProtTAS PMID: 8034748 basonuclin-1, protein from Homo sapiens BNIPL HUMANSplice Isoform 1 of Bcl- UniProt IDA PMID: 11741952 2/adenovirus E1B 19kDa- interacting protein 2-like protein, protein from Homo sapiens BRCA1HUMAN Breast cancer type 1 UniProt TAS PMID: 10918303 susceptibilityprotein, protein from Homo sapiens BRCA2 HUMAN Breast cancer type 2UniProt IDA PMID: 9560268 susceptibility protein, protein from Homosapiens BRD1 HUMAN Bromodomain-containing UniProt TAS PMID: 10602503protein 1, protein from Homo sapiens BRD3 HUMAN Splice Isoform 1 ofUniProt NAS UniProt: Q15059 Bromodomain-containing protein 3, proteinfrom Homo sapiens BRD8 HUMAN Splice Isoform 1 of UniProt NAS PMID:8611617 Bromodomain-containing protein 8, protein from Homo sapiensBRPF1 HUMAN Peregrin, protein from UniProt TAS PMID: 7906940 Homosapiens BRSK1 HUMAN Splice Isoform 1 of BR UniProt IDA PMID: 15150265serine/threonine-protein kinase 1, protein from Homo sapiens BSN HUMANBassoon protein, protein UniProt TAS PMID: 9806829 from Homo sapiensBT3L2 HUMAN Transcription factor BTF3 UniProt NAS UniProt: Q13891homolog 2, protein from Homo sapiens BT3L3 HUMAN Transcription factorBTF3 UniProt NAS UniProt: Q13892 homolog 3, protein from Homo sapiensBTAF1 HUMAN TATA-binding-protein- UniProt NAS UniProt: O14981 associatedfactor 172, protein from Homo sapiens BTG1 HUMAN BTG1 protein, proteinUniProt IMP PMID: 11420681 from Homo sapiens IEP PMID: 9820826 CABINHUMAN Calcineurin-binding UniProt NAS UniProt: Q9Y6J0 protein Cabin 1,protein from Homo sapiens CAF1B HUMAN Chromatin assembly UniProt NASPMID: 9614144 factor 1 subunit B, protein from Homo sapiens CARM1 HUMANSplice Isoform 1 of UniProt IDA PMID: 15221992 Histone-argininemethyltransferase CARM1, protein from Homo sapiens CASC5 HUMAN SpliceIsoform 1 of UniProt IDA PMID: 10980622 Cancer susceptibility candidategene 5 protein, protein from Homo sapiens CASL HUMAN Enhancer offilamentation UniProt TAS PMID: 8668148 1, protein from Homo sapiens CBPHUMAN CREB-binding protein, UniProt TAS PMID: 7913207 protein from Homosapiens CBX2 HUMAN Splice Isoform 1 of UniProt NAS UniProt: Q14781Chromobox protein homolog 2, protein from Homo sapiens CBX3 HUMANChromobox protein UniProt TAS PMID: 8663349 homolog 3, protein from Homosapiens CBX4 HUMAN Chromobox homolog 4, UniProt TAS PMID: 9315667protein from Homo sapiens CC14A HUMAN Splice Isoform 1 of Dual UniProtTAS PMID: 9367992 specificity protein phosphatase CDC14A, protein fromHomo sapiens CC14B HUMAN Splice Isoform 2 of Dual UniProt IDA PMID:9367992 specificity protein phosphatase CDC14B, protein from Homosapiens CC45L HUMAN CDC45-related protein, UniProt TAS PMID: 9660782protein from Homo sapiens CCNE1 HUMAN Splice Isoform E1L of UniProt NASUniProt: P24864 G1/S-specific cyclin-E1, protein from Homo sapiens CCNHHUMAN Cyclin-H, protein from UniProt TAS PMID: 7936635 Homo sapiens CCP1HUMAN Calcipressin 1 large UniProt TAS PMID: 8595418 isoform, proteinfrom Homo sapiens CD2A1 HUMAN Splice Isoform 1 of UniProt NR UniProt:P42771 Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3, proteinfrom Homo sapiens CD2L1 HUMAN Splice Isoform SV9 of UniProt IEP PMID:8195233 PITSLRE serine/threonine-protein kinase CDC2L1, protein fromHomo sapiens CD2L2 HUMAN Splice Isoform SV6 of UniProt IEP PMID: 8195233PITSLRE serine/threonine-protein kinase CDC2L2, protein from Homosapiens CD2L7 HUMAN Cell division cycle 2- UniProt IDA PMID: 11683387related protein kinase 7, protein from Homo sapiens CDC2 HUMANHypothetical protein UniProt TAS PMID: 10767298 DKFZp686L20222, proteinfrom Homo sapiens CDC6 HUMAN Cell division control UniProt TAS PMID:9566895 protein 6 homolog, protein from Homo sapiens CDC7 HUMAN Celldivision cycle 7- UniProt TAS PMID: 9250678 related protein kinase,protein from Homo sapiens CDCA5 HUMAN Sororin, protein from UniProt ISSUniProt: Q96FF9 Homo sapiens CDK1 HUMAN Cyclin-dependent kinase UniProtTAS PMID: 9506968 2-associated protein 1, protein from Homo sapiens CDK2HUMAN Cell division protein UniProt TAS PMID: 10767298 kinase 2, proteinfrom Homo sapiens CDK5 HUMAN Cell division protein UniProt ISS UNIPROT:Q00535 kinase 5, protein from Homo sapiens CDK7 HUMAN Cell divisionprotein UniProt TAS PMID: 7936635 kinase 7, protein from Homo sapiensCDK9 HUMAN Splice Isoform 1 of Cell UniProt TAS PMID: 8170997 divisionprotein kinase 9, protein from Homo sapiens CDN1A HUMAN Cyclin-dependentkinase UniProt TAS PMID: 9660939 inhibitor 1, protein from Homo sapiensCDN1B HUMAN Cyclin-dependent kinase UniProt IDA PMID: 12093740 inhibitor1B, protein from Homo sapiens CDN2C HUMAN Cyclin-dependent kinase 6UniProt NR UniProt: P42773 inhibitor, protein from Homo sapiens CDN2DHUMAN Cyclin-dependent kinase 4 UniProt TAS PMID: 8741839 inhibitor D,protein from Homo sapiens CDR2 HUMAN Cerebellar degeneration- UniProtNAS UniProt: Q13977 related protein 2, protein from Homo sapiens CDT1HUMAN DNA replication factor UniProt IDA PMID: 11125146 Cdt1, proteinfrom Homo sapiens CEBPA HUMAN CCAAT/enhancer binding UniProt NAS PMID:7575576 protein alpha, protein from Homo sapiens CEBPB HUMANCCAAT/enhancer binding UniProt TAS PMID: 10821850 protein beta, proteinfrom Homo sapiens CEBPG HUMAN CCAAT/enhancer binding UniProt ISS PMID:7501458 protein gamma, protein from Homo sapiens CEBPZ HUMANCCAAT/enhancer binding UniProt TAS PMID: 2247079 protein zeta, proteinfrom Homo sapiens CENA1 HUMAN Centaurin-alpha 1, UniProt IDA PMID:10448098 protein from Homo sapiens IDA PMID: 10333475 CENG1 HUMANCentaurin-gamma 1, UniProt ISS PMID: 11136977 protein from Homo sapiensCENPA HUMAN Centromere protein A, UniProt TAS PMID: 7962047 protein fromHomo sapiens CENPE HUMAN Centromere protein E, UniProt IMP PMID: 9763420protein from Homo sapiens CEZ1 HUMAN Zinc finger protein UniProt IDAPMID: 11463333 CeZanne, protein from Homo sapiens CHD6 HUMAN SpliceIsoform 1 of UniProt NAS PMID: 12592387 Chromodomain-helicase-DNA-binding protein 6, protein from Homo sapiens CHD8 HUMANChromodomain-helicase- UniProt NAS UniProt: Q9HCK8 DNA-binding protein8, protein from Homo sapiens CHK2 HUMAN Splice Isoform 1 of UniProt NASUniProt: O96017 Serine/threonine-protein kinase Chk2, protein from Homosapiens CITE2 HUMAN Splice Isoform 2 of UniProt NAS PMID: 10552932Cbp/p300-interacting transactivator 2, protein from Homo sapiens CIZ1HUMAN Splice Isoform 1 of Cip1- UniProt TAS PMID: 10529385 interactingzinc finger protein, protein from Homo sapiens CK001 HUMAN ProteinC11orf1, protein UniProt NAS PMID: 10873569 from Homo sapiens CLAT HUMANSplice Isoform M of UniProt TAS PMID: 10861222 Choline O-acetyltransferase, protein from Homo sapiens CLIC2 HUMAN Chlorideintracellular UniProt TAS PMID: 16130169 channel protein 2, protein fromHomo sapiens CLIC3 HUMAN Chloride intracellular UniProt IDA PMID:9880541 channel protein 3, protein from Homo sapiens CN004 HUMAN ProteinC14orf4, protein UniProt NAS PMID: 11095982 from Homo sapiens CND1 HUMANCondensin complex UniProt NAS PMID: 10958694 subunit 1, protein fromHomo sapiens CND3 HUMAN Condensin complex UniProt NAS PMID: 10910072subunit 3, protein from Homo sapiens CNOT2 HUMAN Splice Isoform 1 ofUniProt NAS PMID: 10637334 CCR4-NOT transcription complex subunit 2,protein from Homo sapiens CNOT7 HUMAN CCR4-NOT transcription UniProt IEPPMID: 9820826 complex subunit 7, protein from Homo sapiens CNOT8 HUMANCCR4-NOT transcription UniProt NAS PMID: 10036195 complex subunit 8,protein from Homo sapiens COF1 HUMAN Cofilin, non-muscle UniProt TASPMID: 16130169 isoform, protein from Homo sapiens COT2 HUMAN COUPtranscription factor UniProt TAS PMID: 1899293 2, protein from Homosapiens CREB1 HUMAN Splice Isoform CREB-A UniProt TAS PMID: 10909971 ofcAMP response element binding protein, protein from Homo sapiens CREB3HUMAN Splice Isoform 1 of Cyclic UniProt NAS PMID: 9271389AMP-responsive element binding protein 3, protein from Homo sapiensCREB5 HUMAN Splice Isoform 1 of cAMP UniProt IC PMID: 8378084 responseelement-binding protein 5, protein from Homo sapiens CREM HUMAN CAMPresponsive UniProt NAS UniProt: Q16114 element modulator, protein fromHomo sapiens CRK HUMAN Splice Isoform Crk-II of UniProt TAS PMID:10748058 Proto-oncogene C-crk, protein from Homo sapiens CRNL1 HUMANCrn, crooked neck-like 1, UniProt NAS UniProt: Q9BZI9 protein from Homosapiens CRSP2 HUMAN CRSP complex subunit 2, UniProt IDA PMID: 10235267protein from Homo sapiens CRSP6 HUMAN CRSP complex subunit 6, UniProtIDA PMID: 10235267 protein from Homo sapiens CRYAB HUMAN Alphacrystallin B chain, UniProt NR UniProt: P02511 protein from Homo sapiensCSDC2 HUMAN Cold shock domain UniProt NAS UniProt: Q9Y534 protein C2,protein from Homo sapiens CSE1 HUMAN Splice Isoform 1 of UniProt TASPMID: 9323134 Importin-alpha re- exporter, protein from Homo sapiensCSR2B HUMAN Splice Isoform 1 of UniProt IPI PMID: 10924333 Cysteine-richprotein 2 binding protein, protein from Homo sapiens CSRP2 HUMANCysteine and glycine-rich UniProt NAS PMID: 96215313 protein 2, proteinfrom Homo sapiens CSTF1 HUMAN Cleavage stimulation UniProt TAS PMID:1358884 factor, 50 kDa subunit, protein from Homo sapiens CSTF2 HUMANSplice Isoform 1 of UniProt TAS PMID: 1741396 Cleavage stimulationfactor, 64 kDa subunit, protein from Homo sapiens CSTF3 HUMAN Cleavagestimulation UniProt TAS PMID: 7984242 factor, 77 kDa subunit, proteinfrom Homo sapiens CTCF HUMAN Transcriptional repressor UniProt IDA PMID:9407128 CTCF, protein from Homo sapiens CTDS1 HUMAN Carboxy-terminaldomain UniProt TAS PMID: 10967134 RNA polymerase II polypeptide A smallphosphatase 1, protein from Homo sapiens CTNB1 HUMAN Splice Isoform 1 ofBeta- UniProt TAS PMID: 9065401 catenin, protein from Homo sapiens CTND1HUMAN Splice Isoform 1ABC of UniProt NAS PMID: 98317528 Catenin delta-1,protein from Homo sapiens CUGB1 HUMAN Splice Isoform 2 of CUG UniProtNAS PMID: 10893231 triplet repeat RNA- binding protein 1, protein fromHomo sapiens CUTL2 HUMAN Homeobox protein cut- UniProt NAS UniProt:O14529 like 2, protein from Homo sapiens CX4NB HUMAN Neighbor of COX4,UniProt TAS PMID: 10337626 protein from Homo sapiens CXCC1 HUMAN CpGbinding protein, UniProt IDA PMID: 10688657 protein from Homo sapiensDAPK3 HUMAN Death-associated protein UniProt ISS UniProt: O43293 kinase3, protein from Homo sapiens DAXX HUMAN Splice Isoform 1 of DeathUniProt IDA PMID: 15572661 domain-associated protein 6, protein fromHomo sapiens DCTN4 HUMAN Dynactin subunit 4, UniProt TAS PMID: 10671518protein from Homo sapiens DDX17 HUMAN Splice Isoform 1 of UniProt TASPMID: 8871553 Probable ATP-dependent RNA helicase DDX17, protein fromHomo sapiens DDX39 HUMAN ATP-dependent RNA UniProt ISS PMID: 15047853helicase DDX39, protein from Homo sapiens DDX3X HUMAN ATP-dependent RNAUniProt IDA PMID: 10329544 helicase DDX3X, protein from Homo sapiensDDX54 HUMAN ATP-dependent RNA UniProt ISS UniProt: Q9BRZ1 helicaseDDX54, protein from Homo sapiens IDA PMID: 12466272 DDX5 HUMAN ProbableATP-dependent UniProt NAS PMID: 2451786 RNA helicase DDX5, protein fromHomo sapiens DEAF1 HUMAN Splice Isoform 1 of UniProt TAS PMID: 9773984Deformed epidermal autoregulatory factor 1 homolog, protein from Homosapiens DEK HUMAN Protein DEK, protein UniProt TAS PMID: 9050861 fromHomo sapiens DFFA HUMAN Splice Isoform DFF45 of UniProt IDA PMID:15572351 DNA fragmentation factor alpha subunit, protein from Homosapiens DFFB HUMAN Splice Isoform Alpha of UniProt IDA PMID: 15572351DNA fragmentation factor 40 kDa subunit, protein from Homo sapiens DGC14HUMAN DGCR14 protein, protein UniProt ISS PMID: 8703114 from Homosapiens DGCR8 HUMAN Splice Isoform 1 of UniProt IDA PMID: 15574589 DGCR8protein, protein from Homo sapiens DGKI HUMAN Diacylglycerol kinase,UniProt TAS PMID: 9830018 iota, protein from Homo sapiens DGKZ HUMANSplice Isoform Long of UniProt TAS PMID: 9716136 Diacylglycerol kinase,zeta, protein from Homo sapiens DHRS2 HUMAN Dehydrogenase/reductase,UniProt TAS PMID: 7556196 protein from Homo sapiens DHX15 HUMAN Putativepre-mRNA UniProt TAS PMID: 9388478 splicing factor ATP- dependent RNAhelicase DHX15, protein from Homo sapiens DHX16 HUMAN Putative pre-mRNAUniProt TAS PMID: 9547260 splicing factor ATP- dependent RNA helicaseDHX16, protein from Homo sapiens DHX9 HUMAN DEAH (Asp-Glu-Ala-His)UniProt TAS PMID: 9111062 box polypeptide 9 isoform 1, protein from Homosapiens DLG7 HUMAN Splice Isoform 2 of Discs UniProt IDA PMID: 12527899large homolog 7, protein from Homo sapiens DLX1 HUMAN Homeobox proteinDLX- UniProt NAS UniProt: P56177 1, protein from Homo sapiens DMAP1HUMAN DNA methyltransferase 1- UniProt NAS PMID: 10888872 associatedprotein 1, protein from Homo sapiens DNJC1 HUMAN DnaJ homolog subfamilyUniProt ISS UniProt: Q96KC8 C member 1, protein from Homo sapiens DNL1HUMAN DNA ligase I, protein UniProt TAS PMID: 8696349 from Homo sapiensDNL3 HUMAN Ligase III, DNA, ATP- UniProt TAS PMID: 7565692 dependent,isoform alpha, protein from Homo sapiens DNL4 HUMAN DNA ligase IV,protein UniProt TAS PMID: 8798671 from Homo sapiens DNM3A HUMAN DNA,protein from Homo UniProt ISS PMID: 12138111 sapiens DNM3B HUMAN SpliceIsoform 1 of DNA, UniProt TAS PMID: 10433969 protein from Homo sapiensDNM3L HUMAN DNA (cytosine-5)- UniProt NAS PMID: 12202768methyltransferase 3-like, protein from Homo sapiens DNMT1 HUMAN SpliceIsoform 1 of DNA, UniProt TAS PMID: 8940105 protein from Homo sapiensDP13A HUMAN DCC-interacting protein UniProt IDA PMID: 15016378 13 alpha,protein from Homo sapiens DP13B HUMAN DCC-interacting protein UniProtIDA PMID: 15016378 13 beta, protein from Homo sapiens DPF3 HUMANZinc-finger protein UniProt NAS UniProt: Q92784 DPF3, protein from Homosapiens DPOA2 HUMAN DNA polymerase alpha UniProt NAS UniProt: Q14181subunit B, protein from Homo sapiens DPOD2 HUMAN DNA polymerase deltaUniProt TAS PMID: 8530069 subunit 2, protein from Homo sapiens DPOD4HUMAN DNA polymerase delta UniProt TAS PMID: 10751307 subunit 4, proteinfrom Homo sapiens DPOE3 HUMAN DNA polymerase epsilon UniProt TAS PMID:10801849 subunit 3, protein from Homo sapiens DPOE4 HUMAN DNA polymeraseepsilon UniProt TAS PMID: 10801849 subunit 4, protein from Homo sapiensDPOLA HUMAN DNA polymerase alpha UniProt NAS UniProt: P09884 catalyticsubunit, protein from Homo sapiens DPOLL HUMAN DNA polymerase UniProtNAS PMID: 10982892 lambda, protein from Homo sapiens DRBP1 HUMAN SpliceIsoform 1 of UniProt IDA PMID: 12220514 Developmentally regulatedRNA-binding protein 1, protein from Homo sapiens DRR1 HUMAN DRR1protein, protein UniProt IDA PMID: 10564580 from Homo sapiens DSRADHUMAN Splice Isoform 1 of UniProt TAS PMID: 7565688 Double-stranded RNA-specific adenosine deaminase, protein from Homo sapiens DTBP1 HUMANSplice Isoform 1 of UniProt ISS UniProt: Q96EV8 Dystrobrevin-bindingprotein 1, protein from Homo sapiens DUS10 HUMAN Dual specificityprotein UniProt TAS PMID: 10391943 phosphatase 10, protein from Homosapiens DUS11 HUMAN Splice Isoform 1 of UniProt TAS PMID: 9685386RNA/RNP complex-1 intereracting phosphatase, protein from Homo sapiensDUS16 HUMAN Dual specificity protein UniProt TAS PMID: 11489891phosphatase 16, protein from Homo sapiens DUS21 HUMAN Dual specificityprotein UniProt IDA PMID: 12408986 phosphatase 21, protein from Homosapiens DUS2 HUMAN Dual specificity protein UniProt TAS PMID: 8107850phosphatase 2, protein from Homo sapiens DUS4 HUMAN Dual specificityprotein UniProt TAS PMID: 7535768 phosphatase 4, protein from Homosapiens DUS9 HUMAN Dual specificity protein UniProt TAS PMID: 9030581phosphatase 9, protein from Homo sapiens DUT HUMAN Splice Isoform DUT-Mof UniProt TAS PMID: 8631816 Deoxyuridine 5′- triphosphatenucleotidohydrolase, mitochondrial precursor, protein from Homo sapiensDYR1A HUMAN Splice Isoform Long of UniProt IDA PMID: 9748265 Dualspecificity tyrosine- phosphorylation regulated kinase 1A, protein fromHomo sapiens DYR1B HUMAN Splice Isoform 1 of Dual UniProt TAS PMID:9918863 specificity tyrosine- phosphorylation regulated kinase 1B,protein from Homo sapiens DZIP1 HUMAN Splice Isoform 1 of Zinc UniProtIDA PMID: 15081113 finger protein DZIP1, protein from Homo sapiens ECM29HUMAN PREDICTED: KIAA0368 UniProt IDA PMID: 15496406 protein, proteinfrom Homo sapiens EDD1 HUMAN Ubiquitin--protein ligase UniProt IDA PMID:12011095 EDD1, protein from Homo sapiens EDF1 HUMAN Splice Isoform 1 ofUniProt IDA PMID: 10567391 Endothelial differentiation-related factor 1,protein from Homo sapiens EGF HUMAN Pro-epidermal growth UniProt NRUniProt: P01133 factor precursor, protein from Homo sapiens EGFR HUMANSplice Isoform 1 of UniProt IDA PMID: 12828935 Epidermal growth factorreceptor precursor, protein from Homo sapiens EGLN2 HUMAN Egl ninehomolog 2, UniProt IDA PMID: 11850811 protein from Homo sapiens EHD2HUMAN Similar to EH-domain UniProt TAS PMID: 10673336 containing protein2, protein from Homo sapiens EHD3 HUMAN EH-domain containing UniProt TASPMID: 10673336 protein 3, protein from Homo sapiens EHD4 HUMAN EH-domaincontaining UniProt TAS PMID: 10673336 protein 4, protein from Homosapiens EHMT1 HUMAN Splice Isoform 2 of UniProt IC PMID: 12004135Histone-lysine N- methyltransferase, H3 lysine-9 specific 5, proteinfrom Homo sapiens ELF1 HUMAN ETS-related transcription UniProt NASUniProt: P32519 factor Elf-1, protein from Homo sapiens ELF2 HUMANSplice Isoform 1 of ETS- UniProt IC PMID: 14970218 related transcriptionfactor Elf-2, protein from Homo sapiens ELL3 HUMAN RNA polymerase IIUniProt IDA PMID: 10882741 elongation factor ELL3, protein from Homosapiens EMX1 HUMAN Homeobox protein UniProt NAS UniProt: Q04741 EMX1,protein from Homo sapiens EMX2 HUMAN Homeobox protein UniProt NASUniProt: Q04743 EMX2, protein from Homo sapiens ENC1 HUMANEctoderm-neural cortex 1 UniProt TAS PMID: 9566959 protein, protein fromHomo sapiens ENL HUMAN ENL protein, protein UniProt TAS PMID: 8080983from Homo sapiens EP300 HUMAN E1A-associated protein UniProt IDA PMID:9194565 p300, protein from Homo sapiens EPC1 HUMAN Splice Isoform 1 ofUniProt IDA PMID: 10976108 Enhancer of polycomb homolog 1, protein fromHomo sapiens ERCC2 HUMAN TFIIH basal transcription UniProt NAS UniProt:P18074 factor complex helicase subunit, protein from Homo sapiens ERCC3HUMAN TFIIH basal transcription UniProt TAS PMID: 8663148 factor complexhelicase XPB subunit, protein from Homo sapiens ERG HUMAN Splice IsoformERG-2 of UniProt TAS PMID: 8502479 Transcriptional regulator ERG,protein from Homo sapiens ERR1 HUMAN Steroid hormone receptor UniProtTAS PMID: 9286700 ERR1, protein from Homo sapiens ERR3 HUMAN SpliceIsoform 1 of UniProt ISS UniProt: P62508 Estrogen-related receptorgamma, protein from Homo sapiens ESR2 HUMAN Splice Isoform 1 of UniProtTAS PMID: 11181953 Estrogen receptor beta, protein from Homo sapiensETV3 HUMAN Splice Isoform 1 of ETS UniProt NAS UniProt: P41162translocation variant 3, protein from Homo sapiens ETV4 HUMAN ETStranslocation variant UniProt NAS UniProt: P43268 4, protein from Homosapiens ETV7 HUMAN Splice Isoform B of UniProt TAS PMID: 10828014Transcription factor ETV7, protein from Homo sapiens EVI1 HUMAN SpliceIsoform 1 of UniProt NAS UniProt: Q03112 Ecotropic virus integration 1site protein, protein from Homo sapiens EVX2 HUMAN Homeobox even-skippedUniProt NAS UniProt: Q03828 homolog protein 2, protein from Homo sapiensEXOS2 HUMAN Exosome complex UniProt TAS PMID: 8600032 exonuclease RRP4,protein from Homo sapiens FA50A HUMAN Protein FAM50A, protein UniProtTAS PMID: 9339379 from Homo sapiens FAF1 HUMAN Splice Isoform Long ofUniProt IDA PMID: 15596450 FAS-associated factor 1, protein from Homosapiens FALZ HUMAN Fetal Alzheimer antigen, UniProt IDA PMID: 10727212protein from Homo sapiens FANCA HUMAN Splice Isoform 1 of UniProt TASPMID: 9398857 Fanconi anemia group A protein, protein from Homo sapiensFANCC HUMAN Fanconi anemia group C UniProt TAS PMID: 9398857 protein,protein from Homo sapiens FANCE HUMAN Fanconi anemia group E UniProt NASPMID: 11001585 protein, protein from Homo sapiens FANCJ HUMAN SpliceIsoform 1 of UniProt NAS PMID: 11301010 Fanconi anemia group J protein,protein from Homo sapiens FGF10 HUMAN Fibroblast growth factor UniProtIDA PMID: 11923311 10 precursor, protein from Homo sapiens FHL2 HUMANFHL2 isoform 5, protein UniProt TAS PMID: 9150430 from Homo sapiensFHOD1 HUMAN FH1/FH2 domain- UniProt TAS PMID: 10352228 containingprotein, protein from Homo sapiens FIBP HUMAN Splice Isoform Short ofUniProt TAS PMID: 9806903 Acidic fibroblast growth factor intracellularbinding protein, protein from Homo sapiens FIZ1 HUMAN Flt3-interactingzinc UniProt ISS UniProt: Q96SL8 finger protein 1, protein from Homosapiens FMR1 HUMAN Splice Isoform 6 of UniProt TAS PMID: 8515814 FragileX mental retardation 1 protein, protein from Homo sapiens FOS HUMANProto-oncogene protein c- UniProt TAS PMID: 9443941 fos, protein fromHomo sapiens FOSL1 HUMAN Fos-related antigen 1, UniProt TAS PMID:10918580 protein from Homo sapiens FOSL2 HUMAN Fos-related antigen 2,UniProt TAS PMID: 8954781 protein from Homo sapiens FOXC1 HUMAN Forkheadbox protein C1, UniProt NAS UniProt: Q9BYM1 protein from Homo sapiensFOXD3 HUMAN Forkhead box protein D3, UniProt ISS UniProt: Q9UJU5 proteinfrom Homo sapiens FOXD4 HUMAN Forkhead box protein D4, UniProt NASUniProt: O43638 protein from Homo sapiens FOXE3 HUMAN Forkhead boxprotein E3, UniProt NAS UniProt: Q13461 protein from Homo sapiens FOXF1HUMAN Forkhead box protein F1, UniProt TAS PMID: 9722567 protein fromHomo sapiens FOXF2 HUMAN Forkhead box protein F2, UniProt TAS PMID:9722567 protein from Homo sapiens FOXGC HUMAN Forkhead box proteinUniProt NAS UniProt: Q14488 G1C, protein from Homo sapiens FOXI1 HUMANForkhead box I1 isoForm UniProt NAS UniProt: Q12951 a, protein from Homosapiens FOXJ1 HUMAN Forkhead box protein J1, UniProt TAS PMID: 9073514protein from Homo sapiens FOXK2 HUMAN Splice Isoform 1 of UniProt TASPMID: 1909027 Forkhead box protein K2, protein from Homo sapiens FOXL1HUMAN Forkhead box protein L1, UniProt NAS UniProt: Q12952 protein fromHomo sapiens FOXL2 HUMAN FOXL2, protein from UniProt NAS UniProt: P58012Homo sapiens FOXN1 HUMAN Forkhead box protein N1, UniProt TAS PMID:10767081 protein from Homo sapiens FOXO3 HUMAN Forkhead box proteinUniProt TAS PMID: 10102273 O3A, protein from Homo sapiens FOXO4 HUMANSplice Isoform 1 of UniProt TAS PMID: 9010221 Putative fork head domaintranscription factor AFX1, protein from Homo sapiens FOXP3 HUMAN SpliceIsoform 1 of UniProt NAS UniProt: Q9BZS1 Forkhead box protein P3,protein from Homo sapiens FREA HUMAN Forkhead-related UniProt NASUniProt: O43638 transcription factor 10, protein from Homo sapiens FRKHUMAN Tyrosine-protein kinase UniProt TAS PMID: 7696183 FRK, proteinfrom Homo sapiens FUBP3 HUMAN Splice Isoform 2 of Far UniProt NAS PMID:8940189 upstream element-binding protein 3, protein from Homo sapiensFUS HUMAN Fus-like protein, protein UniProt TAS PMID: 8510758 from Homosapiens FUSIP HUMAN Splice Isoform 1 of FUS- UniProt ISS UniProt: Q96P17interacting serine- arginine-rich protein 1, protein from Homo sapiensIC PMID: 9774382 FXL10 HUMAN Splice Isoform 1 of F- UniProt NAS PMID:10799292 box/LRR-repeat protein 10, protein from Homo sapiens FXR2 HUMANFragile X mental UniProt TAS PMID: 10888599 retardation syndrome-related protein 2, protein from Homo sapiens FYB HUMAN Splice IsoformFYB-120 UniProt TAS PMID: 9207119 of FYN-binding protein, protein fromHomo sapiens G10 HUMAN G10 protein homolog, UniProt TAS PMID: 7841202protein from Homo sapiens G3BP HUMAN Ras-GTPase-activating UniProt TASPMID: 9889278 protein binding protein 1, protein from Homo sapiens GA45AHUMAN Growth arrest and DNA- UniProt TAS PMID: 7798274 damage-inducibleprotein GADD45 alpha, protein from Homo sapiens GABP2 HUMAN SpliceIsoform 1 of GA UniProt TAS PMID: 9016666 binding protein beta chain,protein from Homo sapiens GABPA HUMAN GA binding protein alpha UniProtTAS PMID: 9016666 chain, protein from Homo sapiens GATA1 HUMAN SpliceIsoform 1 of UniProt TAS PMID: 2300555 Erythroid transcription factor,protein from Homo sapiens GATA2 HUMAN Endothelial transcription UniProtTAS PMID: 1370462 factor GATA-2, protein from Homo sapiens GATA4 HUMANTranscription factor UniProt NAS PMID: 12845333 GATA-4, protein fromHomo sapiens GCFC HUMAN Splice Isoform A of GC- UniProt NAS UniProt:Q9Y5B6 rich sequence DNA- binding factor homolog, protein from Homosapiens GCM1 HUMAN Chorion-specific UniProt TAS PMID: 8962155transcription factor GCMa, protein from Homo sapiens GCM2 HUMANChorion-specific UniProt TAS PMID: 9928992 transcription factor GCMb,protein from Homo sapiens GCR HUMAN Splice Isoform Alpha of UniProt TASPMID: 9873044 Glucocorticoid receptor, protein from Homo sapiens GLI3HUMAN Zinc finger protein GLI3, UniProt TAS PMID: 10077605 protein fromHomo sapiens GLI4 HUMAN Zinc finger protein GLI4, UniProt NAS UniProt:P10075 protein from Homo sapiens GLIS1 HUMAN Zinc finger protein UniProtISS UniProt: Q8NBF1 GLIS1, protein from Homo sapiens GLIS3 HUMAN Zincfinger protein UniProt ISS UniProt: Q8NEA6 GLIS3, protein from Homosapiens GLRX2 HUMAN Splice Isoform 1 of UniProt IEP PMID: 11297543Glutaredoxin-2, mitochondrial precursor, protein from Homo sapiens GMEB1HUMAN Splice Isoform 1 of UniProt TAS PMID: 10386584 Glucocorticoidmodulatory element- binding protein 1, protein from Homo sapiens GMEB2HUMAN Glucocorticoid UniProt TAS PMID: 10523663 modulatory element-binding protein 2, protein from Homo sapiens GNEFR HUMAN Splice Isoform2 of UniProt IDA PMID: 10571079 Guanine nucleotide exchangefactor-related protein, protein from Homo sapiens GNL3 HUMAN SpliceIsoform 1 of UniProt ISS UniProt: Q9BVP2 Guanine nucleotide bindingprotein-like 3, protein from Homo sapiens GO45 HUMAN Splice Isoform 1 ofUniProt NAS PMID: 9129147 Golgin 45, protein from Homo sapiens GRAAHUMAN Granzyme A precursor, UniProt TAS PMID: 11909973 protein from Homosapiens GRAB HUMAN Endogenous granzyme B, UniProt TAS PMID: 11909973protein from Homo sapiens GRLF1 HUMAN Glucocorticoid receptor UniProt ICPMID: 1894621 DNA bindinG factor 1 isoform b, protein from Homo sapiensGRP78 HUMAN 78 kDa glucose-regulated UniProt IDA PMID: 12665508 proteinprecursor, protein from Homo sapiens GSC HUMAN Homeobox protein UniProtNAS UniProt: P56915 goosecoid, protein from Homo sapiens GT2D1 HUMANSplice Isoform 1 of UniProt NAS PMID: 11438732 General transcriptionfactor II-I repeat domain- containing protein 1, protein from Homosapiens H2AFX HUMAN Histone H2A.x, protein UniProt IDA PMID: 15604234from Homo sapiens IDA PMID: 11331621 HAIR HUMAN Splice Isoform 1 ofUniProt NAS PMID: 9445480 Hairless protein, protein from Homo sapiensHASP HUMAN Splice Isoform 1 of UniProt IEP PMID: 11228240Serine/threonine-protein kinase Haspin, protein from Homo sapiens HAT1HUMAN Histone acetyltransferase UniProt TAS PMID: 9427644 type Bcatalytic subunit, protein from Homo sapiens HBXAP HUMAN Remodeling andspacing UniProt IDA PMID: 12972596 factoR 1, protein from Homo sapiensIDA PMID: 11788598 HCC1 HUMAN Nuclear protein Hcc-1, UniProt NAS PMID:11356193 protein from Homo sapiens HCFC1 HUMAN Splice Isoform 1 of HostUniProt IDA PMID: 7876203 cell factor, protein from Homo sapiens HCFC2HUMAN Host cell factor 2, protein UniProt IDA PMID: 10196288 from Homosapiens HDA10 HUMAN Splice Isoform 1 of UniProt IDA PMID: 11861901Histone deacetylase 10, protein from Homo sapiens HDA11 HUMAN Histonedeacetylase 11, UniProt IDA PMID: 11948178 protein from Homo sapiensHDAC1 HUMAN Histone deacetylase 1, UniProt TAS PMID: 12711221 proteinfrom Homo sapiens HDAC2 HUMAN Histone deacetylase 2, UniProt TAS PMID:12711221 protein from Homo sapiens HDAC3 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 12711221 Histone deacetylase 3, protein from Homosapiens HDAC4 HUMAN Histone deacetylase 4, UniProt NAS UniProt: P56524protein from Homo sapiens HDAC5 HUMAN Splice Isoform 1 of UniProt TASPMID: 12711221 Histone deacetylase 5, protein from Homo sapiens HDAC6HUMAN Histone deacetylase 6, UniProt NAS UNIPROT: Q9UBN7 protein fromHomo sapiens HDAC7 HUMAN Histone deacetylase, UniProt TAS PMID: 12711221protein from Homo sapiens HDAC9 HUMAN Splice Isoform 1 of UniProt NASUniProt: Q9UKV0 Histone deacetylase 9, protein from Homo sapiens HDGR3HUMAN Hepatoma-derived growth UniProt IDA PMID: 10581169 factor-relatedprotein 3, protein from Homo sapiens HD HUMAN Huntingtin, protein fromUniProt TAS PMID: 9778247 Homo sapiens HELI HUMAN Splice Isoform 1 ofZinc UniProt NAS UniProt: Q9UKS7 finger protein Helios, protein fromHomo sapiens HIC1 HUMAN Splice Isoform 2 of UniProt NAS UniProt: Q14526Hypermethylated in cancer 1 protein, protein from Homo sapiens HIC2HUMAN Splice Isoform 1 of UniProt IEP PMID: 11554746 Hypermethylated incancer 2 protein, protein from Homo sapiens HIF1A HUMANHypoxia-inducible factor UniProt IDA PMID: 15261140 1 alpha, proteinfrom Homo sapiens HINT1 HUMAN Histidine triad nucleotide- UniProt TASPMID: 9770345 binding protein 1, protein from Homo sapiens HIPK2 HUMANSplice Isoform 1 of UniProt IDA PMID: 12220523 Homeodomain-interactingprotein kinase 2, protein from Homo sapiens HIPK3 HUMAN Splice Isoform 1of UniProt IDA PMID: 11034606 Homeodomain-interacting protein kinase 3,protein from Homo sapiens HIRA HUMAN Splice Isoform Long of UniProt TASPMID: 9710638 HIRA protein, protein from Homo sapiens HIRP3 HUMAN SpliceIsoform 1 of UniProt TAS PMID: 9710638 HIRA-interacting protein 3,protein from Homo sapiens HKR1 HUMAN Krueppel-related zinc UniProt NASUniProt: P10072 finger protein 1, protein from Homo sapiens HKR2 HUMANKrueppel-related zinc UniProt NAS UniProt: P10073 finger protein 2,protein from Homo sapiens HLF HUMAN Hepatic leukemia factor, UniProt TASPMID: 1386162 protein from Homo sapiens HLXB9 HUMAN Homeobox proteinHB9, UniProt NAS UniProt: P50219 protein from Homo sapiens NAS UniProt:Q9Y648 HM20B HUMAN SWI/SNF-related matrix- UniProt NAS UniProt: Q9P0W2associated actin- dependent regulator of chromatin subfamily E member1-related, protein from Homo sapiens HM2L1 HUMAN High mobility groupUniProt NAS UniProt: Q9UGU5 protein 2-like 1, protein from Homo sapiensHMG17 HUMAN Nonhistone chromosomal UniProt NAS UniProt: P05204 proteinHMG-17, protein from Homo sapiens HMG1 HUMAN High mobility group UniProtTAS PMID: 16130169 protein 1, protein from Homo sapiens HMGN3 HUMAN Highmobility group UniProt NAS UniProt: Q15651 nucleosome binding domain 3,protein from Homo sapiens HNF1B HUMAN Splice Isoform A of UniProt TASPMID: 1677179 Hepatocyte nuclear factor 1-beta, protein from Homosapiens HNF3G HUMAN Hepatocyte nuclear factor UniProt TAS PMID: 77398973-gamma, protein from Homo sapiens HNF4A HUMAN Hepatocyte nuclear factorUniProt TAS PMID: 9048927 4 alpHa isoform b, protein from Homo sapiensHNF6 HUMAN Hepatocyte nuclear factor UniProt NAS UniProt: Q9UBC0 6,protein from Homo sapiens HNRPD HUMAN Splice Isoform 1 of UniProt NASPMID: 1433497 Heterogeneous nuclear ribonucleoprotein D0, protein fromHomo sapiens HNRPQ HUMAN Splice Isoform 1 of UniProt TAS PMID: 9847309Heterogeneous nuclear ribonucleoprotein Q, protein from Homo sapiens HRXHUMAN Splice Isoform 1 of Zinc UniProt IDA PMID: 11313484 finger proteinHRX, protein from Homo sapiens HS74L HUMAN Heat shock 70 kDa UniProt ISSUniProt: O95757 protein 4L, protein from Homo sapiens HSBP1 HUMAN Heatshock factor binding UniProt TAS PMID: 9649501 protein 1, protein fromHomo sapiens HSP71 HUMAN Heat shock 70 kDa UniProt TAS PMID: 10205060protein 1, protein from Homo sapiens HTRA2 HUMAN Splice Isoform 1 ofSerine UniProt TAS PMID: 10971580 protease HTRA2, mitochondrialprecursor, protein from Homo sapiens HUWE1 HUMAN Splice Isoform 1 ofUniProt ISS UniProt: Q7Z6Z7 HECT, UBA and WWE domain containing protein1, protein from Homo sapiens HXA5 HUMAN Homeobox protein Hox- UniProtNAS UniProt: P20719 A5, protein from Homo sapiens HXB1 HUMAN Homeoboxprotein Hox- UniProt NAS UniProt: P14653 B1, protein from Homo sapiensHXB4 HUMAN Homeobox protein Hox- UniProt NAS UniProt: P17483 B4, proteinfrom Homo sapiens HXB6 HUMAN Splice Isoform 1 of UniProt NAS UniProt:P17509 Homeobox protein Hox- B6, protein from Homo sapiens HXB7 HUMANHomeobox protein Hox- UniProt NAS PMID: 1678287 B7, protein from Homosapiens HXB8 HUMAN Homeobox protein Hox- UniProt NAS UniProt: P17481 B8,protein from Homo sapiens HXB9 HUMAN Homeobox protein Hox- UniProt NASUniProt: P17482 B9, protein from Homo sapiens HXC13 HUMAN Homeoboxprotein Hox- UniProt NAS UniProt: P31276 C13, protein from Homo sapiensHXC4 HUMAN Homeobox protein Hox- UniProt NAS UniProt: P09017 C4, proteinfrom Homo sapiens HXC8 HUMAN Homeobox protein Hox- UniProt NAS UniProt:P31273 C8, protein from Homo sapiens HXD11 HUMAN Homeobox protein Hox-UniProt NAS UniProt: P31277 D11, protein from Homo sapiens HXD4 HUMANHomeobox protein Hox- UniProt NAS UniProt: P09016 D4, protein from Homosapiens HXD8 HUMAN Homeobox protein Hox- UniProt NAS PMID: 2568311 D8,protein from Homo sapiens IASPP HUMAN Splice Isoform 1 of RelA- UniProtTAS PMID: 10336463 associated inhibitor, protein from Homo sapiens IF16HUMAN Splice Isoform 2 of UniProt IDA PMID: 7536752 Gamma-interferon-inducible protein Ifi-16, protein from Homo sapiens IF6 HUMAN Eukaryotictranslation UniProt TAS PMID: 9374518 initiation factor 6, protein fromHomo sapiens IKBA HUMAN NF-kappaB inhibitor UniProt IDA PMID: 7679069alpha, protein from Homo sapiens ILF2 HUMAN Interleukin enhancer-UniProt IDA PMID: 7519613 binding factor 2, protein from Homo sapiensILF3 HUMAN Splice Isoform 1 of UniProt IDA PMID: 11739746 Interleukinenhancer- binding factor 3, protein from Homo sapiens NAS PMID: 10400669IMA2 HUMAN Importin alpha-2 subunit, UniProt TAS PMID: 9020106 proteinfrom Homo sapiens IMB3 HUMAN Importin beta-3, protein UniProt TAS PMID:9114010 from Homo sapiens IMUP HUMAN Similar to UniProt TAS PMID:11080599 Immortalization- upregulated protein, protein from Homo sapiensIN35 HUMAN Splice Isoform 1 of UniProt IDA PMID: 8288566Interferon-induced 35 kDa protein, protein from Homo sapiens ING1 HUMANSplice Isoform 1 of UniProt NAS PMID: 10866301 Inhibitor of growthprotein 1, protein from Homo sapiens ING2 HUMAN Inhibitor of growthUniProt IEP PMID: 15243141 protein 2, protein from Homo sapiens ING4HUMAN Splice Isoform 1 of UniProt IDA PMID: 15029197 Inhibitor of growthprotein 4, protein from Homo sapiens IP6K1 HUMAN Inositol hexaphosphateUniProt TAS PMID: 11502751 kinase 1, protein from Homo sapiens IP6K2HUMAN Splice Isoform 1 of UniProt ISS UniProt: Q9UHH9 Inositolhexakisphosphate kinase 2, protein from Homo sapiens IP6K3 HUMANInositol hexaphosphate UniProt IDA PMID: 11502751 kinase 3, protein fromHomo sapiens ISS UniProt: Q96PC2 IRF4 HUMAN Splice Isoform 1 of UniProtIC PMID: 12374808 Interferon regulatory factor 4, protein from Homosapiens IRF7 HUMAN Splice Isoform A of UniProt ISS UniProt: Q92985Interferon regulatory factor 7, protein from Homo sapiens IRS1 HUMANInsulin receptor substrate UniProt ISS UniProt: P35568 1, protein fromHomo sapiens IRTF HUMAN Transcriptional regulator UniProt TAS PMID:1630447 ISGF3 gamma subunit, protein from Homo sapiens ITF2 HUMAN SpliceIsoform SEF2-1B UniProt TAS PMID: 1681116 of Transcription factor 4,protein from Homo sapiens JAD1A HUMAN Jumonji/ARID domain- UniProt TASPMID: 8414517 containing protein 1A, protein from Homo sapiens JERKLHUMAN Jerky homolog-like, UniProt TAS PMID: 9240447 protein from Homosapiens KCY HUMAN UMP-CMP kinase, UniProt TAS PMID: 10462544 proteinfrom Homo sapiens KIF22 HUMAN Kinesin-like protein UniProt TAS PMID:8599929 KIF22, protein from Homo sapiens KLF10 HUMAN Transforming growthUniProt TAS PMID: 9748269 factor-beta-inducible early growth responseprotein 1, protein from Homo sapiens KLF11 HUMAN Transforming growthUniProt TAS PMID: 9748269 factor-beta-inducible early growth responseprotein 2, protein from Homo sapiens KLF2 HUMAN Kruppel-like factor 2,UniProt NAS UniProt: Q9Y5W3 protein from Homo sapiens KLF4 HUMANKruppel-like factor 4, UniProt ISS PMID: 9422764 protein from Homosapiens KLF6 HUMAN Splice Isoform 1 of Core UniProt TAS PMID: 9689109promoter element-binding protein, protein from Homo sapiens KNTC1 HUMANKinetochore-associated UniProt NAS PMID: 11146660 protein 1, proteinfrom Homo sapiens KPCI HUMAN Protein kinase C, iota UniProt ISS UniProt:P41743 type, protein from Homo sapiens KR18 HUMAN Zinc finger proteinKr18, UniProt NAS UniProt: Q9HCG1 protein from Homo sapiens KS6A2 HUMANRibosomal protein S6 UniProt TAS PMID: 7623830 kinase alpha 2, proteinfrom Homo sapiens KS6A4 HUMAN Ribosomal protein S6 UniProt IEP PMID:9792677 kinase alpha 4, protein from Homo sapiens ISS UniProt: O75585IDA PMID: 11035004 KS6A5 HUMAN Ribosomal protein S6 UniProt IEP PMID:9687510 kinase alpha 5, protein from Homo sapiens KU70 HUMANATP-dependent DNA UniProt TAS PMID: 10508516 helicase II, 70 kDasubunit, protein from Homo sapiens KU86 HUMAN ATP-dependent DNA UniProtTAS PMID: 7957065 helicase II 80 kDa subunit, protein from Homo sapiensLANC2 HUMAN LanC-like protein 2, UniProt IDA PMID: 12566319 protein fromHomo sapiens LAP2 HUMAN Splice Isoform 1 of LAP2 UniProt ISS PMID:11375975 protein, protein from Homo sapiens IDA PMID: 11375975 LATS2HUMAN Serine/threonine-protein UniProt NAS PMID: 10673337 kinase LATS2,protein from Homo sapiens LDOC1 HUMAN Protein LDOC1, protein UniProt TASPMID: 10403563 from Homo sapiens LEG3 HUMAN LGALS3 protein, proteinUniProt IDA PMID: 14961764 from Homo sapiens LHX3 HUMAN Splice Isoform Aof UniProt TAS PMID: 10598593 LIM/homeobox protein Lhx3, protein fromHomo sapiens LIMK2 HUMAN Splice Isoform LIMK2a UniProt TAS PMID: 8954941of LIM domain kinase 2, protein from Homo sapiens LMBL2 HUMAN SpliceIsoform 1 of UniProt NAS UniProt: Q969R5 Lethal(3)malignant braintumor-like 2 protein, protein from Homo sapiens LMBL3 HUMAN SpliceIsoform 1 of UniProt NAS UniProt: Q96JM7 Lethal(3)malignant braintumor-like 3 protein, protein from Homo sapiens LMO7 HUMAN SpliceIsoform 3 of LIM UniProt TAS PMID: 9826547 domain only protein 7,protein from Homo sapiens LMX1B HUMAN Splice Isoform Short of UniProtNAS UniProt: O60663 LIM homeobox transcription factor 1 beta, proteinfrom Homo sapiens IDA PMID: 10767331 LPIN1 HUMAN Lipin-1, protein fromUniProt ISS PMID: 11138012 Homo sapiens LPPRC HUMAN 130 kDa leucine-richUniProt IDA PMID: 12832482 protein, protein from Homo sapiens ISSUniProt: P42704 LSM1 HUMAN U6 snRNA-associated UniProt TAS PMID:10369684 Sm-like protein LSm1, protein from Homo sapiens LSM2 HUMAN U6snRNA-associated UniProt NAS UniProt: Q9Y333 Sm-like protein LSm2,protein from Homo sapiens LSM3 HUMAN U6 snRNA-associated UniProt TASPMID: 10369684 Sm-like protein LSm3, protein from Homo sapiens LSM5HUMAN U6 snRNA-associated UniProt TAS PMID: 10369684 Sm-like proteinLSm5, protein from Homo sapiens LSM7 HUMAN U6 snRNA-associated UniProtNAS UNIPROT: Q9UK45 Sm-like protein LSm7, protein from Homo sapiens LSM8HUMAN U6 snRNA-associated UniProt NAS UniProt: O95777 Sm-like proteinLSm8, protein from Homo sapiens LZTS1 HUMAN Leucine zipper, putativeUniProt NAS UniProt: Q9Y5V7 tumor suppressor 1, protein from Homosapiens NAS UniProt: Q9Y5W2 NAS UniProt: Q9Y5W1 NAS UniProt: Q9Y5W0 NASUniProt: Q9Y5V8 MAD HUMAN MAD protein, protein UniProt TAS PMID: 8425218from Homo sapiens MAFB HUMAN Transcription factor UniProt TAS PMID:8001130 MafB, protein from Homo sapiens MAGC2 HUMAN Melanoma-associatedUniProt IDA PMID: 12920247 antigen C2, protein from Homo sapiens MAGE1HUMAN Melanoma-associated UniProt ISS PMID: 14623885 antigen E1, proteinfrom Homo sapiens MAML1 HUMAN Mastermind-like protein UniProt IDA PMID:11101851 1, protein from Homo sapiens MAML2 HUMAN MasterMind-like 2,UniProt IDA PMID: 12370315 protein from Homo sapiens MAML3 HUMANMasterMind-like 3, UniProt IDA PMID: 12370315 protein from Homo sapiensMAPK2 HUMAN Splice Isoform 1 of MAP UniProt TAS PMID: 8280084kinase-activated protein kinase 2, protein from Homo sapiens MAPK3 HUMANMAP kinase-activated UniProt TAS PMID: 10781029 protein kinase 3,protein from Homo sapiens MBB1A HUMAN Splice Isoform 1 of Myb- UniProtISS UniProt: Q9BQG0 binding protein 1A, protein from Homo sapiens MBD1HUMAN Splice Isoform 1 of UniProt NAS PMID: 10454587 Methyl-CpG-bindingdomain protein 1, protein from Homo sapiens MBD2 HUMAN Splice Isoform 1of UniProt NAS PMID: 10441743 Methyl-CpG-binding domain protein 2,protein from Homo sapiens MBD4 HUMAN Splice Isoform 1 of UniProt TASPMID: 9774669 Methyl-CpG-binding domain protein 4, protein from Homosapiens MBNL HUMAN Splice Isoform EXP35 of UniProt IDA PMID: 10970838Muscleblind-like protein, protein from Homo sapiens MCA3 HUMANEukaryotic translation UniProt ISS UniProt: O43324 elongation factor 1epsilon-1, protein from Homo sapiens MCE1 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9473487 mRNA capping enzyme, protein from Homo sapiensMCM2 HUMAN DNA replication licensing UniProt TAS PMID: 8175912 factorMCM2, protein from Homo sapiens MCM3A HUMAN 80 kda MCM3-associatedUniProt TAS PMID: 9712829 protein, protein from Homo sapiens MCM4 HUMANDNA replication licensing UniProt NAS PMID: 8265339 factor MCM4, proteinfrom Homo sapiens MCM5 HUMAN DNA replication licensing UniProt TAS PMID:8751386 factor MCM5, protein from Homo sapiens MCM6 HUMAN DNAreplication licensing UniProt NAS PMID: 9286856 factor MCM6, proteinfrom Homo sapiens MD2BP HUMAN MAD2L1 binding UniProt IDA PMID: 10942595protein, protein from Homo sapiens MDC1 HUMAN Splice Isoform 1 ofUniProt IDA PMID: 15604234 Mediator of DNA damage checkpoint protein 1,protein from Homo sapiens MDM4 HUMAN Mdm4 protein, protein UniProt NASPMID: 9226370 from Homo sapiens MDN1 HUMAN Midasin, protein from UniProtNAS PMID: 12102729 Homo sapiens MECP2 HUMAN Methyl-CpG-binding UniProtTAS PMID: 10773092 protein 2, protein from Homo sapiens MECT1 HUMANSplice Isoform 1 of UniProt IDA PMID: 14506290 Mucoepidermoid carcinomatranslocated protein 1, protein from Homo sapiens MED12 HUMAN Mediatorof RNA UniProt IDA PMID: 10235267 polymerase II transcription subunit12, protein from Homo sapiens MED4 HUMAN Mediator complex subunitUniProt IDA PMID: 10235267 4, protein from Homo sapiens MED6 HUMAN RNApolymerase UniProt TAS PMID: 10024883 transcriptional regulationmediator, subunit 6 homolog, protein from Homo sapiens MEF2A HUMANSplice Isoform MEF2 of UniProt TAS PMID: 1516833 Myocyte-specificenhancer factor 2A, protein from Homo sapiens MEF2B HUMANMyocyte-specific UniProt TAS PMID: 1516833 enhancer factor 2B, proteinfrom Homo sapiens MEFV HUMAN Splice Isoform 1 of Pyrin, UniProt IDAPMID: 11115844 protein from Homo sapiens MEN1 HUMAN Splice Isoform 1 ofUniProt IDA PMID: 15199122 Menin, protein from Homo sapiens MERL HUMANSplice Isoform 1 of UniProt IDA PMID: 10401006 Merlin, protein from Homosapiens MGMT HUMAN Methylated-DNA-- UniProt TAS PMID: 2188979protein-cysteine methyltransferase, protein from Homo sapiens MGN HUMANMago nashi protein UniProt NAS UniProt: P61326 homolog, protein fromHomo sapiens MITF HUMAN Splice Isoform A2 of UniProt NAS PMID: 9647758Microphthalmia- associated transcription factor, protein from Homosapiens NAS PMID: 10578055 MK14 HUMAN Mitogen-activated protein UniProtISS UniProt: Q16539 kinase 14 isoforM 2, protein from Homo sapiens MKL2HUMAN Splice Isoform 1 of UniProt IC PMID: 14565952 MKL/myocardin-likeprotein 2, protein from Homo sapiens MLH3 HUMAN Splice Isoform 1 of DNAUniProt TAS PMID: 10615123 mismatch repair protein Mlh3, protein fromHomo sapiens MLL2 HUMAN Splice Isoform 1 of UniProt NAS PMID: 9247308Myeloid/lymphoid or mixed-lineage leukemia protein 2, protein from Homosapiens MLL4 HUMAN Splice Isoform 1 of UniProt NAS UniProt: Q9UMN6Myeloid/lymphoid or mixed-lineage leukemia protein 4, protein from Homosapiens MLX HUMAN Splice Isoform Gamma of UniProt IDA PMID: 10918583MAx-like protein X, protein from Homo sapiens MLZE HUMANMelanoma-derived UniProt NAS PMID: 11223543 leucine zipper-containingextranuclear factor, protein from Homo sapiens MO4L1 HUMAN Similar toTestis UniProt NAS UniProt: Q9UBU8 expressed gene 189, protein from Homosapiens MO4L2 HUMAN Mortality factor 4-like UniProt NAS UniProt: Q15014protein 2, protein from Homo sapiens MOL1A HUMAN Mps one binder kinaseUniProt IDA PMID: 15067004 activator-like 1A, protein from Homo sapiensMOS1A HUMAN Splice Isoform 1 of UniProt NAS PMID: 9731530 Molybdenumcofactor biosynthesis protein 1 A, protein from Homo sapiens MPP8 HUMANM-phase phosphoprotein UniProt IDA PMID: 8885239 8, protein from Homosapiens MRE11 HUMAN Splice Isoform 1 of UniProt TAS PMID: 10802669Double-strand break repair protein MRE11A, protein from Homo sapiensMS3L1 HUMAN Splice Isoform 1 of Male- UniProt TAS PMID: 10395802specific lethal 3-like 1, protein from Homo sapiens MSH2 HUMAN DNAmismatch repair UniProt NAS PMID: 7923193 protein Msh2, protein fromHomo sapiens MSH4 HUMAN MutS protein homolog 4, UniProt TAS PMID:9299235 protein from Homo sapiens MSMB HUMAN Splice Isoform PSP94 ofUniProt TAS PMID: 7566962 Beta-microseminoprotein precursor, proteinfrom Homo sapiens MTA70 HUMAN Splice Isoform 1 of N6- UniProt IDA PMID:9409616 adenosine- methyltransferase 70 kDa subunit, protein from Homosapiens MTF1 HUMAN Metal-regulatory UniProt TAS PMID: 3208749transcription factor 1, protein from Homo sapiens MTMR2 HUMANMyotubularin-related UniProt IDA PMID: 12837694 protein 2, protein fromHomo sapiens MUSC HUMAN Musculin, protein from UniProt TAS PMID: 9584154Homo sapiens MUTYH HUMAN Splice Isoform Alpha-1 of UniProt TAS PMID:7823963 A/G-specific adenine DNA glycosylase, protein from Homo sapiensMVP HUMAN Major vault protein, UniProt TAS PMID: 7585126 protein fromHomo sapiens MX2 HUMAN Interferon-induced GTP- UniProt TAS PMID: 8798556binding protein Mx2, protein from Homo sapiens MXI1 HUMAN Splice Isoform1 of MAX UniProt TAS PMID: 8425219 interacting protein 1, protein fromHomo sapiens MYBA HUMAN Myb-related protein A, UniProt NAS PMID: 8058310protein from Homo sapiens MYC HUMAN Myc proto-oncogene UniProt IDA PMID:15994933 protein, protein from Homo sapiens MYCBP HUMAN C-Myc bindingprotein, UniProt TAS PMID: 9797456 protein from Homo sapiens MYCN HUMANN-myc proto-oncogene UniProt TAS PMID: 3796607 protein, protein fromHomo sapiens MYF6 HUMAN Myogenic factor 6, UniProt TAS PMID: 2311584protein from Homo sapiens MYOD1 HUMAN Myoblast determination UniProt TASPMID: 3175662 protein 1, protein from Homo sapiens MYST2 HUMAN Histoneacetyltransferase UniProt TAS PMID: 10438470 MYST2, protein from Homosapiens MYT1 HUMAN Myelin transcription UniProt NAS PMID: 1280325 factor1, protein from Homo sapiens NAB1 HUMAN Splice Isoform Long of UniProtNAS PMID: 8668170 NGFI-A binding protein 1, protein from Homo sapiensNARG1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 12145306 NMDA receptorregulated protein 1, protein from Homo sapiens IDA PMID: 12140756 NARGLHUMAN Splice Isoform 1 of UniProt ISS UniProt: Q6N069 NMDA receptorregulated 1-like protein, protein from Homo sapiens NASP HUMAN SpliceIsoform 1 of UniProt TAS PMID: 1426632 Nuclear autoantigenic spermprotein, protein from Homo sapiens NCBP2 HUMAN Nuclear cap bindingUniProt NAS PMID: 7651522 protein subunit 2, protein from Homo sapiensNCOA1 HUMAN Splice Isoform 1 of UniProt TAS PMID: 9223431 Nuclearreceptor coactivator 1, protein from Homo sapiens NCOA2 HUMAN Nuclearreceptor UniProt NAS UniProt: Q15596 coactivator 2, protein from Homosapiens NCOA3 HUMAN Splice Isoform 1 of UniProt NAS PMID: 97410321Nuclear receptor coactivator 3, protein from Homo sapiens NAS UniProt:Q9UPC9 NCOA4 HUMAN Splice Isoform Alpha of UniProt TAS PMID: 8643607Nuclear receptor coactivator 4, protein from Homo sapiens NCOA6 HUMANNuclear receptor UniProt IDA PMID: 11443112 coactivator 6, protein fromHomo sapiens NAS PMID: 10567404 NCOR2 HUMAN Nuclear receptor co- UniProtTAS PMID: 10097068 repressor 2, protein from Homo sapiens NDKA HUMANNucleoside diphosphate UniProt NAS UniProt: P15531 kinase A, proteinfrom Homo sapiens TAS PMID: 16130169 NDKB HUMAN Nucleoside diphosphateUniProt NAS UniProt: P22392 kinase B, protein from Homo sapiens NEDD8HUMAN NEDD8 precursor, UniProt TAS PMID: 9353319 protein from Homosapiens NEK1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 15604234Serine/threonine-protein kinase Nek1, protein from Homo sapiens NEK3HUMAN Serine/threonine-protein UniProt NAS PMID: 7522034 kinase Nek3,protein from Homo sapiens NELFE HUMAN Splice Isoform 1 of UniProt NASPMID: 2119325 Negative elongation factor E, protein from Homo sapiensNFAC2 HUMAN Splice Isoform C of UniProt TAS PMID: 8668213 Nuclear factorof activated T-cells, cytoplasmic 2, protein from Homo sapiens NFAT5HUMAN Splice Isoform C of UniProt TAS PMID: 10051678 Nuclear factor ofactivated T cells 5, protein from Homo sapiens NFE2 HUMAN Transcriptionfactor NF- UniProt TAS PMID: 7774011 E2 45 kDa subunit, protein fromHomo sapiens NFIA HUMAN Nuclear factor 1 A-type, UniProt NAS PMID:7590749 protein from Homo sapiens NFIB HUMAN Splice Isoform 1 of UniProtTAS PMID: 7590749 Nuclear factor 1 B-type, protein from Homo sapiensNFKB2 HUMAN Splice Isoform 1 of UniProt IDA PMID: 15677444 Nuclearfactor NF-kappa- B p100 subunit, protein from Homo sapiens NFS1 HUMANCysteine desulfurase, UniProt TAS PMID: 9885568 mitochondrial precursor,protein from Homo sapiens NFYA HUMAN Splice Isoform Long of UniProt IDAPMID: 15243141 Nuclear transcription factor Y subunit alpha, proteinfrom Homo sapiens NFYB HUMAN Nuclear transcription UniProt IEP PMID:15243141 factor Y subunit beta, protein from Homo sapiens NFYC HUMANSplice Isoform 3 of UniProt IEP PMID: 15243141 Nuclear transcriptionfactor Y subunit gamma, protein from Homo sapiens NHRF2 HUMAN SpliceIsoform 1 of UniProt TAS PMID: 9054412 Na(+)/H(+) exchange regulatorycofactor NHE- RF2, protein from Homo sapiens NKRF HUMANNF-kappa-B-repressing UniProt IDA PMID: 10562553 factor, protein fromHomo sapiens NKX31 HUMAN Splice Isoform 1 of UniProt NAS PMID: 11137288Homeobox protein Nkx- 3.1, protein from Homo sapiens NLK HUMANSerine/threonine kinase UniProt ISS UniProt: Q9UBE8 NLK, protein fromHomo sapiens NMES1 HUMAN Normal mucosa of UniProt IDA PMID: 12209954esophagus-specific gene 1 protein, protein from Homo sapiens NMNA1 HUMANNicotinamide UniProt IDA PMID: 11248244 mononucleotideadenylyltransferase 1, protein from Homo sapiens NNP1 HUMAN NNP-1protein, protein UniProt TAS PMID: 9192856 from Homo sapiens NOCT HUMANNocturnin, protein from UniProt TAS PMID: 10521507 Homo sapiens NOG2HUMAN Nucleolar GTP-binding UniProt TAS PMID: 8822211 protein 2, proteinfrom Homo sapiens NONO HUMAN Non-POU domain- UniProt TAS PMID: 9360842containing octamer- binding protein, protein from Homo sapiens NOTC1HUMAN Neurogenic locus notch UniProt TAS PMID: 10713164 homolog protein1 precursor, protein from Homo sapiens NOTC2 HUMAN Neurogenic locusnotch UniProt IDA PMID: 1303260 homolog protein 2 precursor, proteinfrom Homo sapiens NOTC4 HUMAN Splice Isoform 1 of UniProt TAS PMID:8681805 Neurogenic locus notch homolog protein 4 precursor, protein fromHomo sapiens NP1L2 HUMAN Nucleosome assembly UniProt TAS PMID: 8789438protein 1-like 2, protein from Homo sapiens NPM2 HUMAN Nucleoplasmin-2,protein UniProt IEP PMID: 12714744 from Homo sapiens NPM HUMANNucleophosmin, protein UniProt IDA PMID: 12080348 from Homo sapiens TASPMID: 16130169 NR1D1 HUMAN Orphan nuclear receptor UniProt TAS PMID:8622974 NR1D1, protein from Homo sapiens NR1D2 HUMAN Orphan nuclearreceptor UniProt TAS PMID: 7997240 NR1D2, protein from Homo sapiensNR1H2 HUMAN Oxysterols receptor LXR- UniProt TAS PMID: 7926814 beta,protein from Homo sapiens NR1H3 HUMAN Splice Isoform 1 of UniProt TASPMID: 7744246 Oxysterols receptor LXR- alpha, protein from Homo sapiensNR2E3 HUMAN Splice Isoform Long of UniProt TAS PMID: 10220376Photoreceptor-specific nuclear receptor, protein from Homo sapiens NR4A2HUMAN Orphan nuclear receptor UniProt TAS PMID: 7877627 NR4A2, proteinfrom Homo sapiens NR4A3 HUMAN Nuclear receptor UniProt NAS PMID: 8634690subfamily 4, group A, member 3 isoform b, protein from Homo sapiensNR5A2 HUMAN Splice Isoform 2 of UniProt TAS PMID: 9786908 Orphan nuclearreceptor NR5A2, protein from Homo sapiens NRIF3 HUMAN Splice Isoform 2of UniProt TAS PMID: 10490654 Nuclear receptor- interacting factor 3,protein from Homo sapiens NRIP1 HUMAN Nuclear receptor- UniProt IDAPMID: 7641693 interacting protein 1, protein from Homo sapiens IDA PMID:12773562 IDA PMID: 11266503 NRL HUMAN Neural retina-specific UniProt TASPMID: 8939891 leucine zipper protein, protein from Homo sapiens NSBP1HUMAN Nucleosomal binding UniProt NAS PMID: 11161810 protein 1, proteinfrom Homo sapiens NSG1 HUMAN Neuron-specific protein UniProt TAS PMID:9013775 family member 1, protein from Homo sapiens NT5C HUMAN SpliceIsoform 1 of 5′(3′)- UniProt TAS PMID: 10702291 deoxyribonucleotidase,cytosolic type, protein from Homo sapiens NTHL1 HUMAN EndonucleaseIII-like UniProt IDA PMID: 12531031 protein 1, protein from Homo sapiensNUMA1 HUMAN Splice Isoform 1 of UniProt TAS PMID: 1541636 Nuclearmitotic apparatus protein 1, protein from Homo sapiens NUPL2 HUMANSplice Isoform 1 of UniProt TAS PMID: 10358091 Nucleoporin-like 2,protein from Homo sapiens NUPR1 HUMAN Nuclear protein 1, protein UniProtIDA PMID: 10092851 from Homo sapiens NVL HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9286697 Nuclear valosin- containing protein-like,protein from Homo sapiens NXF2 HUMAN Nuclear RNA export UniProt ISSUniProt: Q9GZY0 factor 2, protein from Homo sapiens NXF3 HUMAN NuclearRNA export UniProt IDA PMID: 11545741 factor 3, protein from Homosapiens NXF5 HUMAN Splice Isoform A of UniProt IDA PMID: 11566096Nuclear RNA export factor 5, protein from Homo sapiens O00290 AdenovirusE3-14.7K UniProt IDA PMID: 11073942 interacting protein 1, protein fromHomo sapiens O00366 Putative p150, protein UniProt ISS UniProt: O00366from Homo sapiens O14777 Retinoblastoma- UniProt TAS PMID: 9315664associated protein HEC, protein from Homo sapiens O14789 Testis-specificBRDT UniProt TAS PMID: 9367677 protein, protein from Homo sapiens O15125Alternative spliced form UniProt IDA PMID: 9230210 of p15 CDK inhibitor,protein from Homo sapiens O15150 Cerebrin-50, protein from UniProt TASPMID: 9373037 Homo sapiens O15183 Trinucleotide repeat DNA UniProt TASPMID: 8626781 binding protein p20- CGGBP, protein from Homo sapiensO15415 CAGH3, protein from UniProt TAS PMID: 9225980 Homo sapiens O43148MRNA (Guanine-7-) UniProt TAS PMID: 9705270 methyltransferase, proteinfrom Homo sapiens O43245 Protein p65, protein from UniProt NAS PMID:8706045 Homo sapiens O43663 Protein regulating UniProt TAS PMID: 9885575cytokinesis 1, protein from Homo sapiens O43719 HIV TAT specific factorUniProt TAS PMID: 10454543 1, protein from Homo sapiens O43809 Pre-mRNAcleavage UniProt TAS PMID: 9659921 factor I 25 kDa subunit, protein fromHomo sapiens O43812 Homeobox protein UniProt TAS PMID: 9736770 DUX3,protein from Homo sapiens O60519 Cre binding protein-like UniProt TASPMID: 9693048 2, protein from Homo sapiens O60592 Arg/Abl-interactingUniProt TAS PMID: 9211900 protein ArgBP2a, protein from Homo sapiensO60593 SORBS2 protein, protein UniProt NAS PMID: 9211900 from Homosapiens O60671 Cell cycle checkpoint UniProt IC PMID: 9660799 proteinHrad1, protein from Homo sapiens O60870 Kin17 protein, protein UniProtTAS PMID: 1923796 from Homo sapiens O75525 T-Star, protein from UniProtTAS PMID: 10332027 Homo sapiens O75530 Embryonic ectoderm UniProt NASPMID: 9584199 development protein homolog, protein from Homo sapiensO75766 TRIP protein, protein UniProt TAS PMID: 9705290 from Homo sapiensO75799 Transcription repressor, UniProt NAS PMID: 9705290 protein fromHomo sapiens O75805 HOXA-9A, protein from UniProt NAS UniProt: O75805Homo sapiens O75806 HOXA-9B, protein from UniProt NAS UniProt: O75806Homo sapiens O94992 HEXIM1 protein, protein UniProt IDA PMID: 12581153from Homo sapiens O95082 EH-binding protein, UniProt TAS PMID: 10644451protein from Homo sapiens O95133 SOX-29 protein, protein UniProt NASUniProt: O95133 from Homo sapiens O95268 Origin recognition UniProt NASPMID: 9765232 complex subunit ORC5T, protein from Homo sapiens O95273D-type cyclin-interacting UniProt IDA PMID: 12437976 protein 1, proteinfrom Homo sapiens O95391 Step II splicing factor UniProt NR UNIPROT:O95391 SLU7, protein from Homo sapiens O95443 AT rich interactiveUniProt NAS PMID: 10446990 domain 3B (BRIGHT- like) protein, proteinfrom Homo sapiens O95480 Hypothetical protein, UniProt NAS UniProt:O95480 protein from Homo sapiens O95926 Hypothetical protein UniProt NASPMID: 11118353 DKFZp564O2082, protein from Homo sapiens OGT1 HUMANSplice Isoform 2 of UDP- UniProt TAS PMID: 9083067 N-acetylglucosamine--peptide N- acetylglucosaminyltransferase 110 kDa subunit, protein fromHomo sapiens OI106 HUMAN Splice Isoform 1 of 106 kDA UniProt ISSUniProt: Q9UPV9 O-GlcNAc transferase-interacting protein, protein fromHomo sapiens ORC1 HUMAN Origin recognition UniProt TAS PMID: 7502077complex subunit 1, protein from Homo sapiens ORC2 HUMAN Originrecognition UniProt TAS PMID: 8808289 complex subunit 2, protein fromHomo sapiens ORC4 HUMAN Origin recognition UniProt TAS PMID: 9353276complex subunit 4, protein from Homo sapiens ORC5 HUMAN Originrecognition UniProt TAS PMID: 9765232 complex subunit 5, protein fromHomo sapiens OTX1 HUMAN Homeobox protein UniProt NAS UniProt: P32242OTX1, protein from Homo sapiens OTX2 HUMAN Homeobox protein UniProt NASUniProt: P32243 OTX2, protein from Homo sapiens OVOL1 HUMAN Putativetranscription UniProt NAS UniProt: O14753 factor Ovo-like 1, proteinfrom Homo sapiens OZF HUMAN Zinc finger protein OZF, UniProt TAS PMID:8665923 protein from Homo sapiens P53 HUMAN Splice Isoform 1 of UniProtIDA PMID: 7720704 Cellular tumor antigen p53, protein from Homo sapiensP66A HUMAN Splice Isoform 1 of UniProt IDA PMID: 12183469Transcriptional repressor p66 alpha, protein from Homo sapiens ISSUniProt: Q96F28 P73L HUMAN Splice Isoform 1 of UniProt IDA PMID:12446779 Tumor protein p73-like, protein from Homo sapiens P78365Polyhomeotic 2 homolog, UniProt TAS PMID: 9121482 protein from Homosapiens P80C HUMAN Coilin, protein from UniProt TAS PMID: 7971277 Homosapiens PA2G4 HUMAN Proliferation-associated UniProt IDA PMID: 15073182protein 2G4, protein from Homo sapiens PAPOA HUMAN Poly(A) PolymeraseUniProt TAS PMID: 8302877 alPha, protein from Homo sapiens PAR6A HUMANSplice Isoform 1 of UniProt ISS UniProt: Q9NPB6 Partitioning defective 6homolog alpha, protein from Homo sapiens PARK7 HUMAN Protein DJ-1,protein UniProt IDA PMID: 12446870 from Homo sapiens PARN HUMANPoly(A)-specific UniProt TAS PMID: 9736620 ribonuclease PARN, proteinfrom Homo sapiens PARP1 HUMAN Poly [ADP-ribose] UniProt TAS PMID:2513174 polymerase 1, protein from Homo sapiens PARP4 HUMAN Poly[ADP-ribose] UniProt NAS PMID: 10644454 polymerase 4, protein from Homosapiens PARP9 HUMAN Splice Isoform 1 of Poly UniProt TAS PMID: 11110709[ADP-ribose] polymerase 9, protein from Homo sapiens PAWR HUMAN PRKCapoptosis WT1 UniProt NAS UniProt: Q96IZ0 regulator protein, proteinfrom Homo sapiens PAX8 HUMAN Splice Isoform 1 of Paired UniProt NASUniProt: Q16339 box protein Pax-8, protein from Homo sapiens PAX9 HUMANPaired box protein Pax-9, UniProt NAS UniProt: P55771 protein from Homosapiens PBX1 HUMAN Splice Isoform PBX1a of UniProt ISS UniProt: P40424Pre-B-cell leukemia transcription factor 1, protein from Homo sapiensPBX3 HUMAN Splice Isoform PBX3a of UniProt ISS UniProt: P40426Pre-B-cell leukemia transcription factor 3, protein from Homo sapiensPBX4 HUMAN Pre-B-cell leukemia UniProt ISS UniProt: Q9BYU1 transcriPtionfactor 4, protein from Homo sapiens PCAF HUMAN Histone acetyltransferaseUniProt TAS PMID: 10891508 PCAF, protein from Homo sapiens PCBP1 HUMANPoly(rC)-binding protein UniProt NAS UNIPROT: Q15365 1, protein fromHomo sapiens PCBP2 HUMAN Poly(rC)-binding protein UniProt NAS UniProt:Q15366 2, protein from Homo sapiens PDCD8 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9989411 Programmed cell death protein 8, mitochondrialprecursor, protein from Homo sapiens PDZK3 HUMAN Splice Isoform 1 of PDZUniProt ISS PMID: 12671685 domain containing protein 3, protein fromHomo sapiens PEPP1 HUMAN Paired-like homeobox UniProt IDA PMID: 11980563protein PEPP-1, protein from Homo sapiens PERM HUMAN Splice Isoform H17of UniProt TAS PMID: 2829220 Myeloperoxidase precursor, protein fromHomo sapiens PFD5 HUMAN Prefoldin subunit 5, UniProt TAS PMID: 9792694protein from Homo sapiens PFTK1 HUMAN Splice Isoform 1 of UniProt TASPMID: 9202329 Serine/threonine-protein kinase PFTAIRE-1, protein fromHomo sapiens PGEA1 HUMAN Chibby protein, protein UniProt IDA PMID:12712206 from Homo sapiens PGH1 HUMAN Cyclooxygenase 1b3, UniProt ISSUniProt: P23219 protein from Homo sapiens PGH2 HUMAN Prostaglandin G/HUniProt ISS UniProt: P35354 synthase 2 precursor, protein from Homosapiens PHB HUMAN Prohibitin, protein from UniProt TAS PMID: 16130169Homo sapiens PHC1 HUMAN Polyhomeotic-like protein UniProt TAS PMID:9121482 1, protein from Homo sapiens PHF12 HUMAN Splice Isoform 2 of PHDUniProt IDA PMID: 11390640 finger protein 12, protein from Homo sapiensPHF2 HUMAN PHD finger protein 2, UniProt TAS PMID: 10051327 protein fromHomo sapiens PIAS1 HUMAN Protein inhibitor of UniProt TAS PMID: 9724754activated STAT protein 1, protein from Homo sapiens PIAS4 HUMAN Proteininhibitor of UniProt IDA PMID: 11248056 activated STAT protein 4,protein from Homo sapiens NAS PMID: 9724754 PIN1 HUMAN Peptidyl-prolylcis-trans UniProt TAS PMID: 8606777 isomerase NIMA- interacting 1,protein from Homo sapiens PIR HUMAN Pirin, protein from Homo UniProt TASPMID: 9079676 sapiens PKP1 HUMAN Splice Isoform 2 of UniProt NAS PMID:9369526 Plakophilin-1, protein from Homo sapiens PKP2 HUMAN SpliceIsoform 2 of UniProt NAS PMID: 8922383 Plakophilin-2, protein from Homosapiens PLCB1 HUMAN Splice Isoform A of 1- UniProt NAS PMID: 10760467phosphatidylinositol-4,5- bisphosphate phosphodiesterase beta 1, proteinfrom Homo sapiens PML HUMAN Splice Isoform PML-1 of UniProt IDA PMID:9294197 Probable transcription factor PML, protein from Homo sapiensPMS1 HUMAN PMS1 protein homolog 1, UniProt TAS PMID: 8072530 proteinfrom Homo sapiens PMS2 HUMAN Postmeiotic segregation UniProt TAS PMID:8072530 increased 2 nirs variant 2, protein from Homo sapiens PNKP HUMANBifunctional UniProt IDA PMID: 10446193 polynucleotidephosphatase/kinase, protein from Homo sapiens PNRC1 HUMAN Proline-richnuclear UniProt TAS PMID: 7578250 receptor coactivator 1, protein fromHomo sapiens PO2F1 HUMAN Splice Isoform 1 of POU UniProt IDA PMID:11891224 domain, class 2, transcription factor 1, protein from Homosapiens PO5FL HUMAN POU domain, class 5, UniProt TAS UniProt: Q06416transcription factor 1-like protein 1, protein from Homo sapiens PO6F2HUMAN Splice Isoform 1 of POU UniProt IC PMID: 8601806 domain, class 6,transcription factor 2, protein from Homo sapiens POLS HUMAN DNApolymerase sigma, UniProt IDA PMID: 10066793 protein from Homo sapiensPOP7 HUMAN Ribonuclease P protein UniProt TAS PMID: 9630247 subunit p20,protein from Homo sapiens PP2AA HUMAN Serine/threonine protein UniProtNAS PMID: 11007961 phosphatase 2A, catalytic subunit, alpha isoform,protein from Homo sapiens PP2CD HUMAN Protein phosphatase 2C UniProt TASPMID: 9177166 isoform delta, protein from Homo sapiens PP2CE HUMANSplice Isoform 1 of UniProt ISS UniProt: Q96MI6 Protein phosphatase 2Cisoform eta, protein from Homo sapiens PP2CG HUMAN Protein phosphatase2C UniProt TAS PMID: 9271424 isoform gamma, protein from Homo sapiensPP4C HUMAN Serine/threonine protein UniProt NAS UniProt: P60510phosphatase 4 catalytic subunit, protein from Homo sapiens PPARA HUMANPeroxisome proliferator- UniProt TAS PMID: 16271724 activated receptoralpha, protein from Homo sapiens PPARB HUMAN Splice Isoform 1 of UniProtNAS PMID: 11551955 Peroxisome proliferator- activated receptor delta,protein from Homo sapiens PPIE HUMAN Splice Isoform A of UniProt IDAPMID: 11313484 Peptidyl-prolyl cis-trans isomerase E, protein from Homosapiens PPIG HUMAN Splice Isoform 1 of UniProt TAS PMID: 9153302Peptidyl-prolyl cis-trans isomerase G, protein from Homo sapiens PPIL2HUMAN Splice Isoform 1 of UniProt TAS PMID: 8660300 Peptidyl-prolylcis-trans isomerase-like 2, protein from Homo sapiens PPP5 HUMANSerine/threonine protein UniProt TAS PMID: 7925273 phosphatase 5,protein from Homo sapiens PPRB HUMAN Splice Isoform 1 of UniProt IDAPMID: 10235267 Peroxisome proliferator- activated receptor-bindingprotein, protein from Homo sapiens PQBP1 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 10198427 Polyglutamine-binding protein 1, protein fromHomo sapiens PRD15 HUMAN PR-domain zinc finger UniProt NAS UniProt:P57071 protein 15, protein from Homo sapiens PRD16 HUMAN Splice Isoform1 of PR- UniProt IC PMID: 11050005 domain zinc finger protein 16,protein from Homo sapiens PRDM2 HUMAN Splice Isoform 1 of PR- UniProtNAS PMID: 7590293 domain zinc finger protein 2, protein from Homosapiens NAS PMID: 7538672 PREB HUMAN Prolactin regulatory UniProt TASPMID: 10194769 element-binding protein, protein from Homo sapiens PRGC1HUMAN Peroxisome proliferator- UniProt TAS PMID: 12588810 activatedreceptor gamma coactivator 1-alpha, protein from Homo sapiens PRP16HUMAN Pre-mRNA splicing factor UniProt NAS PMID: 9524131 ATP-dependentRNA helicase PRP16, protein from Homo sapiens PRS6A HUMAN 26S proteaseregulatory UniProt TAS PMID: 2194290 subunit 6A, protein from Homosapiens PSA1 HUMAN Splice Isoform Short of UniProt TAS PMID: 7681138Proteasome subunit alpha type 1, protein from Homo sapiens PSA3 HUMANProteasome subunit alpha UniProt TAS PMID: 16130169 type 3, protein fromHomo sapiens PSB4 HUMAN Proteasome subunit beta UniProt TAS PMID:16130169 type 4 precursor, protein from Homo sapiens PSF1 HUMAN DNAreplication complex UniProt IDA PMID: 10942595 GINS protein PSF1,protein from Homo sapiens PTDSR HUMAN Splice Isoform 1 of UniProt IDAPMID: 14729065 Protein PTDSR, protein from Homo sapiens PTHR1 HUMANParathyroid UniProt TAS PMID: 10709993 hormone/parathyroidhormone-related peptide receptor precursor, protein from Homo sapiensPTMA HUMAN Prothymosin alpha, UniProt TAS PMID: 10854063 protein fromHomo sapiens PTMS HUMAN Parathymosin, protein UniProt TAS PMID: 10854063from Homo sapiens PTTG1 HUMAN Securin, protein from UniProt TAS PMID:9811450 Homo sapiens PTTG HUMAN Pituitary tumor- UniProt IDA PMID:10781616 transforming gene 1 protein-interacting protein precursor,protein from Homo sapiens PWP1 HUMAN Periodic tryptophan UniProt TASPMID: 7828893 protein 1 homolog, protein from Homo sapiens Q02313Kruppel-related zinc UniProt NAS UniProt: Q02313 finger protein, proteinfrom Homo sapiens Q03989 ARID5A protein, protein UniProt IC PMID:15640446 from Homo sapiens Q12771 P37 AUF1, protein from UniProt NASPMID: 8246982 Homo sapiens Q12869 R kappa B, protein from UniProt NRUniProt: Q12869 Homo sapiens Q13028 Homeo box protein, UniProt NAS PMID:7647458 protein from Homo sapiens Q13051 Nuclear factor I, proteinUniProt NAS PMID: 8799200 from Homo sapiens Q13127 REST protein, proteinUniProt TAS PMID: 7697725 from Homo sapiens Q13137 NDP52, protein fromUniProt TAS PMID: 7540613 Homo sapiens Q13395 TAR RNA loop bindingUniProt TAS PMID: 8846792 protein, protein from Homo sapiens Q13826Autoantigen, protein UniProt IDA PMID: 7520377 from Homo sapiens Q13862DNA-binding protein, UniProt TAS PMID: 7887923 protein from Homo sapiensQ13901 Hypothetical protein UniProt TAS PMID: 9469821 C1D, protein fromHomo sapiens Q14211 E4BP4 protein, protein UniProt TAS PMID: 7565758from Homo sapiens Q14333 Facioscapulohumeral UniProt NAS UniProt: Q14333muscular dystrophy, protein from Homo sapiens Q14501 HCREM 1alphaprotein, UniProt NAS PMID: 8206879 protein from Homo sapiens Q14503HCREM 2beta-a protein, UniProt NAS PMID: 8206879 protein from Homosapiens Q14548 HOX2.8 protein, protein UniProt IDA PMID: 1871139 fromHomo sapiens Q14561 HPX-5 protein, protein UniProt NAS PMID: 7518789from Homo sapiens Q14655 C-MYC promoter-binding UniProt NAS UniProt:Q14655 protein IRLB, protein from Homo sapiens Q14820 ZFM1 protein,UniProt NAS PMID: 7912130 alternatively spliced product, protein fromHomo sapiens Q14869 MSSP-2 protein, protein UniProt NAS PMID: 7838710from Homo sapiens Q14901 Myc protein, protein from UniProt NAS PMID:2834731 Homo sapiens Q15156 PML-RAR protein, UniProt NAS UniProt: Q15156protein from Homo sapiens Q15170 Pp21 protein, protein UniProt TAS PMID:7971997 from Homo sapiens Q15270 HPX-153 protein, protein UniProt NASUniProt: Q15270 from Homo sapiens Q15288 No distinctive protein UniProtNAS PMID: 8543184 motifs; ORF, protein from Homo sapiens Q15299 RARBprotein, protein UniProt IDA PMID: 2177841 from Homo sapiens Q15325DNA-binding protein, UniProt TAS PMID: 3174636 protein from Homo sapiensQ15327 Nuclear protein, protein UniProt TAS PMID: 7730328 from Homosapiens Q15361 Transcription factor, UniProt NAS PMID: 7597036 proteinfrom Homo sapiens Q15376 Y-chromosome RNA UniProt NAS PMID: 9598316recognition motif protein, protein from Homo sapiens Q15381 Y-chromosomeRNA UniProt TAS PMID: 9598316 recognition motif protein, protein fromHomo sapiens Q15435 Yeast sds22 homolog, UniProt TAS PMID: 7498485protein from Homo sapiens Q15552 CACCC box-binding UniProt TAS PMID:8355710 protein, protein from Homo sapiens Q15574 Hypothetical proteinUniProt NAS PMID: 7801123 TAF1B, protein from Homo sapiens Q15736 Zincfinger protein 223, UniProt NAS UniProt: Q9UMW0 protein from Homosapiens Q15936 Zinc-finger protein, UniProt NAS UniProt: Q15936 proteinfrom Homo sapiens Q16247 Histone H1 transcription UniProt NAS PMID:7969168 factor large subunit 2A, protein from Homo sapiens Q16365 GATA-4transcription UniProt NAS PMID: 7791790 factor, protein from Homosapiens Q16464 Chromosome 17q21 UniProt NAS UniProt: Q16464 mRNA clone694:2., protein from Homo sapiens Q16624 Long overlapping ORF, UniProtNAS PMID: 3265124 protein from Homo sapiens Q16630 HPBRII-4 mRNA,UniProt TAS PMID: 9659921 protein from Homo sapiens Q16670Transcriptional regulator UniProt NAS PMID: 1569959 SCAN domaincontaining protein, protein from Homo sapiens Q5W1B6 OTTHUMP00000028668,UniProt ISS UniProt: Q5W1B6 protein from Homo sapiens Q6ZNA8Hypothetical protein UniProt ISS UniProt: Q6ZNA8 FLJ16262, protein fromHomo sapiens Q7RTV3 ZNF367, protein from UniProt IDA PMID: 15344908 Homosapiens Q86T11 Discs large homolog 7; UniProt ISS UniProt: Q86T11Drosophila Discs large-1 tumor suppressor-like; hepatoma up-regulateDprotein, protein from Homo sapiens Q86TP4 TCFL5 protein, protein UniProtISS UniProt: Q86TP4 from Homo sapiens Q86XB9 BRUNOL4 protein, UniProtISS UniProt: Q86XB9 protein from Homo sapiens Q86XF5 DNA cytosineUniProt ISS PMID: 12138111 methyltransferase 3 alpha, isoform a, proteinfrom Homo sapiens Q86XW5 P621, protein from Homo UniProt IDA PMID:12665582 sapiens Q86YN6 Peroxisome proliferator- UniProt ISS UniProt:Q86YN6 activated receptor gamma coactivator 1beta-1a, protein from Homosapiens Q8IWR7 CGI-121 L1 isoform, UniProt NAS PMID: 12659830 proteinfrom Homo sapiens Q8IXI0 Early hematopoietic zinc UniProt IDA PMID:12393497 finger, protein from Homo sapiens Q8IZV0 DNA cytosine UniProtIDA PMID: 12138111 methyltransferase 3 alpha isoform b, protein fromHomo sapiens Q8N717 KLF4 protein, protein UniProt ISS UniProt: Q8N717from Homo sapiens Q8N9B5 Hypothetical protein UniProt ISS UniProt:Q8N9B5 FLJ37870, protein from Homo sapiens Q8NFW5 Homeoprotein MBX-L,UniProt ISS UniProt: Q8NFW5 protein from Homo sapiens Q8NFW6Homeoprotein MBX-S, UniProt ISS UniProt: Q8NFW6 protein from Homosapiens Q8NHW3 V-maf UniProt IDA PMID: 12368292 musculoaponeuroticfibrosarcoma oncogene homolog A, protein from Homo sapiens Q8TAL0PPARGC1B protein, UniProt ISS UniProt: Q8TAL0 protein from Homo sapiensQ8TD23 TRAF6-binding zinc UniProt IDA PMID: 11751921 finger protein,protein from Homo sapiens Q8TDE4 PGC-1-related estrogen UniProt ISSPMID: 10713165 receptor alpha coactivator short isoform, protein fromHomo sapiens IDA PMID: 11854298 Q8TEY4 Adaptor protein FE65a2, UniProtISS UniProt: Q8TEY4 protein from Homo sapiens Q8WX93 Myoneurin, proteinfrom UniProt IDA PMID: 11598191 Homo sapiens Q8WYA4Brain-muscle-ARNT-like UniProt IDA PMID: 12055078 transcription factor2a, protein from Homo sapiens Q92657 HP8 peptide, protein UniProt NASPMID: 8758458 from Homo sapiens Q92728 RB1 protein, protein from UniProtNAS PMID: 3413073 Homo sapiens Q96BU1 S100P binding protein UniProt IDAPMID: 15632002 Riken, isoform a, protein from Homo sapiens Q96BX9Hypothetical protein UniProt IDA PMID: 15843405 FLJ32915, protein fromHomo sapiens Q96C70 Transcription factor UniProt IDA PMID: 15994933 RAM2splice variant c, protein from Homo sapiens Q96HR3 TRAP/Mediator complexUniProt IDA PMID: 10235267 component TRAP25, protein from Homo sapiensQ96JL8 JADE1L protein, protein UniProt ISS UniProt: Q96JL8 from Homosapiens Q96L96 Muscle alpha-kinase, UniProt ISS UniProt: Q96L96 proteinfrom Homo sapiens Q96MH2 Hypothetical protein UniProt ISS UniProt:Q96MH2 FLJ32384, protein from Homo sapiens Q96S66 Mid-1-related chlorideUniProt ISS PMID: 11279057 channel 1, protein from Homo sapiens Q96SQ1Hypothetical protein UniProt IDA PMID: 12169691 FLJ14714, protein fromHomo sapiens Q99419 ICSAT transcription UniProt ISS UniProt: Q99419factor, protein from Homo sapiens NAS PMID: 8657101 Q99638 RAD9Aprotein, protein UniProt TAS PMID: 8943031 from Homo sapiens Q99718ESE-1a, protein from UniProt NAS PMID: 9234700 Homo sapiens Q9BRV3LOC55974 protein, UniProt IC PMID: 8630032 protein from Homo sapiensQ9BXX3 Breast cancer antigen NY- UniProt NAS PMID: 11280766 BR-1,protein from Homo sapiens Q9BYE0 BHLH factor Hes7, UniProt NAS PMID:11260262 protein from Homo sapiens Q9BYG9 Nucleophosmin/B23.2, UniProtISS UniProt: Q9BYG9 protein from Homo sapiens Q9BYU3 MORF/CBP protein,UniProt NAS PMID: 11157802 protein from Homo sapiens Q9BZ95 Putativechromatin UniProt NAS UniProt: Q9BZ95 modulator, protein from Homosapiens Q9BZC1 Bruno-like 4, RNA UniProt ISS UniProt: Q9BZC1 Bindingprotein; RNA- Binding protein BRUNOL-5; CUG-BP and ETR-3 like factor 4,protein from Homo sapiens Q9BZC2 Trinucleotide repeat UniProt NAS PMID:11158314 containing 4, protein from Homo sapiens Q9BZS0 Kappa B andV(D)J UniProt NAS UniProt: Q9BZS0 recombination signal sequences bindingprotein, protein from Homo sapiens Q9C056 NK6 transcription factorUniProt NAS PMID: 11210186 related, locus 2, protein from Homo sapiensQ9H2G4 CTCL tumor antigen UniProt IDA PMID: 11395479 se20-4, proteinfrom Homo sapiens Q9H2M1 Estrogen receptor alpha, UniProt NAS UniProt:Q9H2M1 protein from Homo sapiens Q9H2M4 Cycle-like factor CLIF, UniProtNAS PMID: 11018023 protein from Homo sapiens Q9H2S9 Zinc fingertranscription UniProt TAS PMID: 10978333 factor Eos, protein from Homosapiens Q9H315 ARTS protein, protein UniProt NAS PMID: 11146656 fromHomo sapiens Q9H4E3 Probable ATP-dependent UniProt NAS PMID: 11024137RNA helicase DDX47, protein from Homo sapiens Q9H509 DJ875K15.1.1,protein UniProt ISS UniProt: Q9H509 from Homo sapiens Q9HB90GTPase-interacting UniProt IDA PMID: 11073942 protein 2, protein fromHomo sapiens Q9HBE0 Beta protein 1 BP1, UniProt NAS PMID: 11069021protein from Homo sapiens Q9HBU2 Lim-homeobox UniProt NAS UniProt:Q9HBU2 transcription factor LHX3, protein from Homo sapiens Q9HD85Pre-B-cell leukemia UniProt NAS PMID: 10825160 transcription factorinteracting protein 1, protein from Homo sapiens Q9NP66 High-mobilitygroup 20A UniProt NAS PMID: 10773667 variant, protein from Homo sapiensQ9NPE2 Mesenchymal stem cell UniProt NAS PMID: 11118320 protein DSC92,protein from Homo sapiens Q9NQL2 OTTHUMP00000016853, UniProt IDA PMID:11073942 protein from Homo sapiens Q9NQL9 Doublesex and mab-3 UniProtNAS UniProt: Q9NQL9 related transcription factor 3, protein from Homosapiens Q9NR48 Ash1, protein from Homo UniProt TAS PMID: 10860993sapiens Q9NR55 Jun dimerization protein UniProt TAS PMID: 10878360p21SNFT, protein from Homo sapiens Q9NS72 K562 cell-derived UniProt NASPMID: 10873651 leucine-zipper-like protein 1, protein from Homo sapiensQ9NX07 Hypothetical protein UniProt ISS UniProt: Q9NX07 FLJ20503,protein from Homo sapiens Q9NYW8 RB-associated KRAB UniProt TAS PMID:10702291 repressor, protein from Homo sapiens Q9NZC4 Ets domaintranscription UniProt ISS UniProt: Q9NZC4 factor, protein from Homosapiens Q9P016 THY28 protein, protein UniProt ISS PMID: 14601557 fromHomo sapiens Q9P112 Chromosome 16 open UniProt NAS PMID: 10570909reading frame 5, protein from Homo sapiens Q9P1Z2 KIAA1536 protein,UniProt ISS UniProt: Q9P1Z2 protein from Homo sapiens Q9P2R9 SRp25nuclear protein UniProt TAS PMID: 10708573 isoform 2, protein from Homosapiens Q9P2S7 Hypothetical protein UniProt NR UniProt: Q9P2S7 FLJ11063,protein from Homo sapiens Q9UC05 22 Kruppel-related zinc UniProt NASUniProt: Q9UC05 finger protein, protein from Homo sapiens Q9UCY6 Nuclearreceptor UniProt NAS PMID: 7479914 subfamily 5, group A, member 1,protein from Homo sapiens Q9UD04 GHDTA = GROWTH UniProt NAS PMID:7642589 hormone gene-derived transcriptional activator/hepatic nuclearfactor-1 alpha homolog, protein from Homo sapiens Q9UD29 Surfactantprotein B- UniProt NAS PMID: 7887923 binding protein, protein from Homosapiens Q9UD78 LBP-1A transcription UniProt TAS PMID: 8114710 factorprotein, protein from Homo sapiens Q9UD83 ATF-A0 transcription UniProtNAS PMID: 8288576 factor protein, protein from Homo sapiens Q9UEP1 Cellcycle checkpoint UniProt ISS UniProt: Q9UEP1 protein, protein from Homosapiens Q9UGK6 Putative secreted ligand, UniProt NR UniProt: Q9UGK6protein from Homo sapiens Q9UGL1 RB-binding protein, UniProt TAS PMID:12657635 protein from Homo sapiens Q9UH59 Bromodomain protein UniProtTAS PMID: 10526152 CELTIX1, protein from Homo sapiens Q9UHK0 Nuclearfragile X mental UniProt TAS PMID: 10556305 retardation proteininteracting protein 1, protein from Homo sapiens Q9ULW3 Basaltranscriptional UniProt TAS PMID: 10648625 activator hABT1, protein fromHomo sapiens Q9UMC5 Zinc finger protein 2, UniProt NAS UniProt: Q9UMC5isoform a, protein from Homo sapiens Q9Y294 ASF1A protein, proteinUniProt NAS PMID: 10759893 from Homo sapiens Q9Y2A1 P53TG1-B, proteinfrom UniProt NAS UniProt: Q9Y2A1 Homo sapiens Q9Y2A2 P53TG1-C, proteinfrom UniProt NAS UniProt: Q9Y2A2 Homo sapiens Q9Y2A3 P53TG1-D, proteinfrom UniProt NAS UniProt: Q9Y2A3 Homo sapiens Q9Y2Y4 Testis zinc fingerprotein, UniProt TAS PMID: 10572087 protein from Homo sapiens Q9Y310CGI-21 protein, protein UniProt NR UniProt: Q9Y310 from Homo sapiensQ9Y3C4 My019 protein, protein UniProt IDA PMID: 12659830 from Homosapiens Q9Y451 Androgen-induced UniProt TAS PMID: 10215036 prostateproliferative shutoff associated protein, protein from Homo sapiensQ9Y474 Zinc-finger motif- UniProt TAS PMID: 9305772 enhancerbinding-protein- 1, protein from Homo sapiens Q9Y489 Centrosomal protein1, UniProt TAS PMID: 10359848 protein from Homo sapiens Q9Y4I0Zinc-finger helicase, UniProt NAS PMID: 9688266 protein from Homosapiens Q9Y586 MAB21L2 protein, UniProt NR UniProt: Q9Y586 protein fromHomo sapiens Q9Y655 Splice Isoform 1 of UniProt TAS PMID: 2601707 Myelinexpression factor 2, protein from Homo sapiens Q9Y664 Actin-associatedprotein UniProt TAS PMID: 1372044 2E4/kaptin, protein from Homo sapiensQ9Y675 SNRPN upstream reading UniProt NAS PMID: 10318933 frame protein,protein from Homo sapiens Q9Y6B2 PTD014, protein from UniProt IDA PMID:11073990 Homo sapiens Q9Y6D4 MORC1 protein, protein UniProt TAS PMID:10369865 from Homo sapiens Q9Y6R2 HUEL, protein from UniProt IDA PMID:10409434 Homo sapiens Q9Y6Z7 Collectin sub-family UniProt ISS PMID:12450124 member 10, protein from Homo sapiens R51A1 HUMAN Splice Isoform1 of UniProt IC PMID: 9396801 RAD51-associated protein 1, protein fromHomo sapiens RA51B HUMAN Splice Isoform 2 of DNA UniProt TAS PMID:9512535 repair protein RAD51 homolog 2, protein from Homo sapiens RA51CHUMAN DNA repair protein UniProt TAS PMID: 9469824 RAD51 homolog 3,protein from Homo sapiens RA51D HUMAN Splice Isoform 1 of DNA UniProtTAS PMID: 9570954 repair protein RAD51 homolog 4, protein from Homosapiens RAB3I HUMAN Splice Isoform 2 of UniProt IDA PMID: 12007189RAB3A-interacting protein, protein from Homo sapiens RAD18 HUMANPostreplication repair UniProt NAS PMID: 10884424 protein RAD18, proteinfrom Homo sapiens RAD51 HUMAN Splice Isoform 1 of DNA UniProt ISSUniProt: Q06609 repair protein RAD51 homolog 1, protein from Homosapiens IDA PMID: 12442171 RAD52 HUMAN RAD52 homolog isoform UniProt TASPMID: 7774919 alpha, protein from Homo sapiens RAD54 HUMAN DNA repairand UniProt TAS PMID: 8805304 recombination protein RAD54-like, proteinfrom Homo sapiens RAE1L HUMAN mRNA-associated protein UniProt TAS PMID:9370289 mrnp 41, protein from Homo sapiens RAG2 HUMAN V(D)Jrecombination- UniProt NAS UniProt: P55895 activating protein 2, proteinfrom Homo sapiens RANB3 HUMAN Splice Isoform 1 of Ran- UniProt TAS PMID:9637251 binding protein 3, protein from Homo sapiens RANB9 HUMAN SpliceIsoform 1 of Ran- UniProt IDA PMID: 12220523 binding protein 9, proteinfrom Homo sapiens RANG HUMAN Ran-specific GTPase- UniProt TAS PMID:16130169 activating protein, protein from Homo sapiens RASF1 HUMANSplice Isoform D of Ras UniProt IEP PMID: 14743218 association domainfamily 1, protein from Homo sapiens RASF7 HUMAN Splice Isoform 1 of RasUniProt NAS UniProt: Q02833 association domain protein 7, protein fromHomo sapiens RB HUMAN Retinoblastoma- UniProt TAS PMID: 3657987associated protein, protein from Homo sapiens RBBP4 HUMAN Chromatinassembly UniProt TAS PMID: 8350924 factor 1 subunit C, protein from Homosapiens RBBP5 HUMAN Retinoblastoma-binding UniProt IDA PMID: 15199122protein 5, protein from Homo sapiens RBBP8 HUMAN RBBP8 protein, proteinUniProt TAS PMID: 10764811 from Homo sapiens RBM10 HUMAN RNA bindingmotif UniProt NAS UniProt: P98175 protein 10, isoform 1, protein fromHomo sapiens RBM5 HUMAN RNA-binding protein 5, UniProt TAS PMID:10352938 protein from Homo sapiens RBM6 HUMAN RNA-binding protein 6,UniProt TAS PMID: 10352938 protein from Homo sapiens RBM8A HUMAN SpliceIsoform 1 of RNA- UniProt NAS PMID: 11013075 binding protein 8A, proteinfrom Homo sapiens NAS PMID: 11030346 RBM9 HUMAN Splice Isoform 1 of RNA-UniProt IDA PMID: 11875103 binding protein 9, protein from Homo sapiensRBX2 HUMAN Splice Isoform 1 of UniProt NAS PMID: 10082581 RING-boxprotein 2, protein from Homo sapiens RBY1A HUMAN RNA-binding motifUniProt TAS PMID: 9598316 protein, Y chromosome, family 1 member A1,protein from Homo sapiens RCL HUMAN c-Myc-responsive protein UniProt TASPMID: 9271375 Rcl, protein from Homo sapiens RD23B HUMAN UV excisionrepair protein UniProt TAS PMID: 8168482 RAD23 homolog B, protein fromHomo sapiens RECQ1 HUMAN ATP-dependent DNA UniProt TAS PMID: 7961977helicase Q1, protein from Homo sapiens RED1 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 8995285 Double-stranded RNA- specific editase 1,protein from Homo sapiens REN3A HUMAN Splice Isoform 1 of UniProt NASPMID: 11163187 Regulator of nonsense transcripts 3A, protein from Homosapiens REN3B HUMAN Splice Isoform 1 of UniProt NAS PMID: 11163187Regulator of nonsense transcripts 3B, protein from Homo sapiens REREHUMAN Splice Isoform 1 of UniProt NAS PMID: 10814707 Arginine-glutamicacid dipeptide repeats protein, protein from Homo sapiens RERG HUMANRas-related and estrogen- UniProt IDA PMID: 11533059 regulated growthinhibitor, protein from Homo sapiens REXO4 HUMAN Splice Isoform 1 of RNAUniProt NAS PMID: 10908561 exonuclease 4, protein from Homo sapiens RFX3HUMAN Splice Isoform 1 of UniProt IC PMID: 12411430 Transcription factorRFX3, protein from Homo sapiens RFX5 HUMAN DNA-binding protein UniProtTAS PMID: 9806546 RFX5, protein from Homo sapiens RHOB HUMAN Rho-relatedGTP-binding UniProt ISS UniProt: P62745 protein RhoB, protein from Homosapiens RING1 HUMAN Polycomb complex UniProt IDA PMID: 9199346 proteinRING1, protein from Homo sapiens RM19 HUMAN 39S ribosomal proteinUniProt IDA PMID: 10942595 L19, mitochondrial precursor, protein fromHomo sapiens RM40 HUMAN 39S ribosomal protein UniProt TAS PMID: 9790763L40, mitochondrial precursor, protein from Homo sapiens RMP HUMAN RNApolymerase II UniProt TAS PMID: 9878255 subunit 5-mediating protein,protein from Homo sapiens RNF14 HUMAN RING finger protein 14, UniProtIDA PMID: 11322894 protein from Homo sapiens RNF4 HUMAN RING fingerprotein 4, UniProt TAS PMID: 9710597 protein from Homo sapiens RNPS1HUMAN Splice Isoform 1 of RNA- UniProt TAS PMID: 9580558 binding proteinwith serine-rich domain 1, protein from Homo sapiens RP14 HUMANRibonuclease P protein UniProt TAS PMID: 10024167 subunit p14, proteinfrom Homo sapiens RP30 HUMAN Ribonuclease P protein UniProt TAS PMID:9630247 subunit p30, protein from Homo sapiens RPB1 HUMAN DNA-directedRNA UniProt NAS PMID: 7622068 polymerase II largest subunit, proteinfrom Homo sapiens RPB8 HUMAN DNA-directed RNA UniProt TAS UniProt:P52434 polymerases I, II, and III 17.1 kDa polypeptide, protein fromHomo sapiens RPGF5 HUMAN Splice Isoform 1 of Rap UniProt IDA PMID:10486569 guanine nucleotide exchange factor 5, protein from Homo sapiensRPP38 HUMAN Ribonuclease P protein UniProt TAS PMID: 9630247 subunitp38, protein from Homo sapiens RPP40 HUMAN Ribonuclease P proteinUniProt TAS PMID: 9630247 subunit p40, protein from Homo sapiens RRP5HUMAN RRP5 protein homolog, UniProt IDA PMID: 14624448 protein from Homosapiens RSSA HUMAN 40S ribosomal protein UniProt TAS PMID: 16130169 SA,protein from Homo sapiens RUNX1 HUMAN Splice Isoform AML-1B UniProt NASUniProt: O60473 of Runt-related transcription factor 1, protein fromHomo sapiens RUNX3 HUMAN Splice Isoform 1 of Runt- UniProt NAS UniProt:Q13761 related transcription factor 3, protein from Homo sapiens RUVB1HUMAN RuvB-like 1, protein from UniProt IDA PMID: 9843967 Homo sapiensRUVB2 HUMAN RuvB-like 2, protein from UniProt IDA PMID: 10524211 Homosapiens S100P HUMAN S-100P protein, protein UniProt IDA PMID: 15632002from Homo sapiens S10AB HUMAN Calgizzarin, protein from UniProt TASPMID: 10851017 Homo sapiens S14L2 HUMAN Splice Isoform 1 of UniProt NASPMID: 11444841 SEC14-like protein 2, protein from Homo sapiens S2A4RHUMAN Splice Isoform 1 of UniProt NAS PMID: 10825161 GLUT4 enhancerfactor DNA binding domain, protein from Homo sapiens SAFB1 HUMANScaffold attachment factor UniProt TAS PMID: 1324173 B, protein fromHomo sapiens SALL2 HUMAN Sal-like protein 2, protein UniProt NASUniProt: Q9Y467 from Homo sapiens SAM68 HUMAN Splice Isoform 1 of KHUniProt IDA PMID: 1374686 domain containing, RNA binding, signaltransduction associated protein 1, protein from Homo sapiens SAS10 HUMANSomething about silencing UniProt ISS UniProt: Q9NQZ2 protein 10,protein from Homo sapiens SATB1 HUMAN DNA-binding protein UniProt TASPMID: 1505028 SATB1, protein from Homo sapiens SCMH1 HUMAN SpliceIsoform 1 of UniProt IC PMID: 10524249 Polycomb protein SCMH1, proteinfrom Homo sapiens SCND1 HUMAN SCAN domain-containing UniProt ISSUniProt: P57086 protein 1, protein from Homo sapiens SCRN1 HUMANSecernin-1, protein from UniProt IDA PMID: 10942595 Homo sapiens SCRT1HUMAN Transcriptional repressor UniProt NAS UniProt: Q9BWW7 scratch 1,protein from Homo sapiens SDCB1 HUMAN Syntenin-1, protein from UniProtNAS PMID: 11179419 Homo sapiens SELB HUMAN Selenocysteine-specificUniProt NAS UniProt: P57772 elongation factor, protein from Homo sapiensSENP1 HUMAN Sentrin/SUMO-specific UniProt TAS PMID: 10652325 protease 1,protein from Homo sapiens SENP7 HUMAN Similar to SUMO-1- UniProt ISSPMID: 10652325 specific protease, protein from Homo sapiens SEPT2 HUMANSeptin-2, protein from UniProt IDA PMID: 10942595 Homo sapiens SEPT7HUMAN Septin-7, protein from UniProt IDA PMID: 15485874 Homo sapiensSESN1 HUMAN Splice Isoform T1 of UniProt TAS PMID: 9926927 Sestrin-1,protein from Homo sapiens SET7 HUMAN Histone-lysine N- UniProt NASUniProt: Q8WTS6 methyltransferase, H3 lysine-4 specific SET7, proteinfrom Homo sapiens SET HUMAN Splice Isoform 1 of SET UniProt IDA PMID:11555662 protein, protein from Homo sapiens SFR11 HUMAN Splicing factorUniProt TAS PMID: 1896467 arginine/serine-rich 11, protein from Homosapiens SFRS2 HUMAN Splicing factor, UniProt IDA PMID: 15652350arginine/serine-rich 2, protein from Homo sapiens SFRS4 HUMAN Splicingfactor, UniProt TAS PMID: 8321209 arginine/serine-rich 4, protein fromHomo sapiens SFRS7 HUMAN Splice Isoform 1 of UniProt TAS PMID: 8013463Splicing factor, arginine/serine-rich 7, protein from Homo sapiens SH3L1HUMAN SH3 domain-binding UniProt TAS PMID: 16130169 glutamicacid-rich-like protein, protein from Homo sapiens SIN3A HUMAN Pairedamphipathic helix UniProt ISS UniProt: Q96ST3 protein Sin3a, proteinfrom Homo sapiens SIP1 HUMAN Zinc finger homeobox UniProt IC PMID:9853615 protein 1b, protein from Homo sapiens SIPA1 HUMAN Signal-inducedUniProt IC PMID: 9183624 proliferation-associated protein 1, proteinfrom Homo sapiens SIRT6 HUMAN Splice Isoform 1 of UniProt ISS UniProt:Q8N6T7 Mono-ADP- ribosyltransferase sirtuin- 6, protein from Homosapiens SKI HUMAN Ski oncogene, protein UniProt NAS UniProt: P12755 fromHomo sapiens SKIL HUMAN Splice Isoform SNON of UniProt ISS UniProt:P12757 Ski-like protein, protein from Homo sapiens SLUG HUMAN Zincfinger protein UniProt TAS PMID: 10866665 SLUG, protein from Homosapiens SMAD1 HUMAN Mothers against UniProt ISS UniProt: Q15797decapentaplegic homolog 1, protein from Homo sapiens NAS PMID: 9759503SMAD2 HUMAN Splice Isoform Long of UniProt ISS UniProt: Q15796 Mothersagainst decapentaplegic homolog 2, protein from Homo sapiens SMAD4 HUMANMothers against UniProt TAS PMID: 10980615 decapentaplegic homolog 4,protein from Homo sapiens SMAD5 HUMAN Mothers against UniProt NAS PMID:9759503 decapentaplegic homolog 5, protein from Homo sapiens SMC1A HUMANStructural maintenance of UniProt IDA PMID: 11076961 chromosome 1-like 1protein, protein from Homo sapiens SMC2 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9789013 Structural maintenance of chromosome 2-like 1protein, protein from Homo sapiens SMC4 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 11850403 Structural maintenance of chromosomes 4-like1 protein, protein from Homo sapiens SMCA1 HUMAN SWI/SNF related, matrixUniProt TAS PMID: 1408766 associated, actin dependent regulator ofchromatin, subfamily a, member 1, protein from Homo sapiens SMCA4 HUMANPossible global UniProt TAS PMID: 8232556 transcription activatorSNF2L4, protein from Homo sapiens SMCA5 HUMAN SWI/SNF-related matrixUniProt IDA PMID: 12972596 associated actin dependent regulator ofchromatin subfamily A member 5, protein from Homo sapiens SMRA3 HUMANSWI/SNF-related matrix- UniProt TAS PMID: 7876228 associated actin-dependent regulator of chromatin subfamily A member 3, protein from Homosapiens SMRD3 HUMAN Splice Isoform 1 of UniProt IDA PMID: 14701856SWI/SNF-related matrix- associated actin- dependent regulator ofchromatin subfamily D member 3, protein from Homo sapiens SMUF2 HUMANSmad ubiquitination UniProt NAS PMID: 11163210 regulatory factor 2,protein from Homo sapiens SND1 HUMAN Staphylococcal nuclease UniProt TASPMID: 7651391 domain-containing protein 1, protein from Homo sapiensSNPC2 HUMAN snRNA-activating protein UniProt TAS PMID: 7715707 complexsubunit 2, protein from Homo sapiens SNPC3 HUMAN snRNA-activatingprotein UniProt TAS PMID: 7715707 complex subunit 3, protein from Homosapiens SNPC5 HUMAN Splice Isoform 1 of UniProt TAS PMID: 9732265snRNA-activating protein complex subunit 5, protein from Homo sapiensSOX15 HUMAN SOX-15 protein, protein UniProt NAS PMID: 8332506 from Homosapiens SOX1 HUMAN SOX-1 protein, protein UniProt NAS PMID: 9337405 fromHomo sapiens SOX21 HUMAN Transcription factor SOX- UniProt NAS PMID:1614875 21, protein from Homo sapiens SOX2 HUMAN Transcription factorSOX- UniProt NAS PMID: 7849401 2, protein from Homo sapiens SOX6 HUMANHMG1/2 (high mobility UniProt NAS PMID: 1614875 group) box familyprotein, protein from Homo sapiens SOX9 HUMAN Transcription factor SOX-UniProt TAS PMID: 10805756 9, protein from Homo sapiens SP100 HUMANSplice Isoform Sp100- UniProt TAS PMID: 2258622 HMG of Nuclearautoantigen Sp-100, protein from Homo sapiens SP110 HUMAN Splice Isoform1 of Sp110 UniProt TAS PMID: 7693701 nuclear body protein, protein fromHomo sapiens SP1 HUMAN Transcription factor Sp1, UniProt NAS UniProt:P08047 protein from Homo sapiens SP3 HUMAN Transcription factor Sp3,UniProt NAS UniProt: Q02447 protein from Homo sapiens SPAST HUMAN SpliceIsoform 1 of UniProt TAS PMID: 10610178 Spastin, protein from Homosapiens SPNXA HUMAN Sperm protein associated UniProt TAS PMID: 10906052with the nucleus on the X chromosome A, protein from Homo sapiens SPNXBHUMAN Sperm protein associated UniProt TAS PMID: 10906052 with thenucleus on the X chromosome B/F, protein from Homo sapiens SPNXC HUMANSperm protein associated UniProt TAS PMID: 10626816 with the nucleus onthe X chromosome C, protein from Homo sapiens SPOP HUMAN Speckle-typePOZ UniProt TAS PMID: 9414087 protein, protein from Homo sapiens SPT6HHUMAN Splice Isoform 1 of UniProt NAS PMID: 8786132 Transcriptionelongation factor SPT6, protein from Homo sapiens SRBS1 HUMAN SpliceIsoform 1 of Sorbin UniProt IDA PMID: 11371513 and SH3 domain-containing protein 1, protein from Homo sapiens SRF HUMAN Serum responsefactor, UniProt TAS PMID: 3203386 protein from Homo sapiens SRPK1 HUMANSplice Isoform 1 of UniProt IDA PMID: 11509566 Serine/threonine-proteinkinase SRPK1, protein from Homo sapiens SRPK2 HUMANSerine/threonine-protein UniProt IDA PMID: 9472028 kinase SRPK2, proteinfrom Homo sapiens SRY HUMAN Sex-determining region Y UniProt NAS PMID:8265659 protein, protein from Homo sapiens NAS PMID: 1425584 SSBP2 HUMANSingle-stranded DNA- UniProt NAS UniProt: P81877 binding protein 2,protein from Homo sapiens SSBP3 HUMAN Splice Isoform 1 of UniProt ISSUniProt: Q9BWW4 Single-stranded DNA- binding protein 3, protein fromHomo sapiens SSF1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 15302935Suppressor of SWI4 1 homolog, protein from Homo sapiens SSNA1 HUMANSjogren's syndrome UniProt TAS PMID: 9430706 nuclear autoantigen 1,protein from Homo sapiens SSX1 HUMAN Protein SSX1, protein UniProt TASPMID: 10072425 from Homo sapiens SSXT HUMAN Splice Isoform 1 of SSXTUniProt TAS PMID: 10072425 protein, protein from Homo sapiens ST17AHUMAN Serine/threonine-protein UniProt IEP PMID: 9786912 kinase 17A,protein from Homo sapiens ST17B HUMAN Serine/threonine-protein UniProtIEP PMID: 9786912 kinase 17B, protein from Homo sapiens ST65G HUMANSplice Isoform 1 of UniProt NAS PMID: 10987294 STAGA complex 65 gammasubunit, protein from Homo sapiens STABP HUMAN STAM-binding protein,UniProt TAS PMID: 10383417 protein from Homo sapiens STAG1 HUMAN Cohesinsubunit SA-1, UniProt TAS PMID: 9305759 protein from Homo sapiens STAG2HUMAN Cohesin subunit SA-2, UniProt TAS PMID: 9305759 protein from Homosapiens STAG3 HUMAN Splice Isoform 1 of UniProt TAS PMID: 10698974Cohesin subunit SA-3, protein from Homo sapiens STAT1 HUMAN SpliceIsoform Alpha of UniProt TAS PMID: 10820245 Signal transducer andactivator of transcription 1-alpha/beta, protein from Homo sapiens STAT3HUMAN Splice Isoform 1 of Signal UniProt TAS PMID: 7512451 transducerand activator of transcription 3, protein from Homo sapiens STF1 HUMANSteroidogenic factor 1, UniProt IDA PMID: 10567391 protein from Homosapiens STIP1 HUMAN Stress-induced- UniProt TAS PMID: 16130169phosphoprotein 1, protein from Homo sapiens STK19 HUMAN Splice Isoform 1of UniProt TAS PMID: 9812991 Serine/threonine-protein kinase 19, proteinfrom Homo sapiens STK38 HUMAN Serine/threonine-protein UniProt IDA PMID:12493777 kinase 38, protein from Homo sapiens STK39 HUMANSTE20/SPS1-related UniProt NAS PMID: 10980603 proline-alanine-richprotein kinase, protein from Homo sapiens STK6 HUMANSerine/threonine-protein UniProt TAS PMID: 9153231 kinase 6, proteinfrom Homo sapiens STRN3 HUMAN Splice Isoform Alpha of UniProt IDA PMID:7910562 Striatin-3, protein from Homo sapiens SUFU HUMAN Splice Isoform1 of UniProt TAS PMID: 10559945 Suppressor of fused homolog, proteinfrom Homo sapiens SUH HUMAN Splice Isoform APCR-2 of UniProt NASUniProt: Q06330 Recombining binding protein suppressor of hairless,protein from Homo sapiens IDA PMID: 9874765 SUPT3 HUMAN Splice Isoform 1of UniProt IEP PMID: 9726987 Transcription initiation protein SPT3homolog, protein from Homo sapiens SUV91 HUMAN Histone-lysine N- UniProtTAS PMID: 10949293 methyltransferase, H3 lysine-9 specific 1, proteinfrom Homo sapiens SVIL HUMAN Splice Isoform 1 of UniProt IDA PMID:12711699 Supervillin, protein from Homo sapiens SYCP2 HUMAN Synaptonemalcomplex UniProt NAS PMID: 10341103 protein 2, protein from Homo sapiensTAD3L HUMAN Splice Isoform 1 of UniProt TAS PMID: 9674425Transcriptional adapter 3- like, protein from Homo sapiens TADBP HUMANTAR DNA-binding UniProt TAS PMID: 7745706 protein 43, protein from Homosapiens TAF1 HUMAN Splice Isoform 1 of UniProt TAS PMID: 7680771Transcription initiation factor TFIID subunit 1, protein from Homosapiens TAF1L HUMAN Transcription initiation UniProt ISS PMID: 12217962factor TFIID 210 kDa subunit, protein from Homo sapiens TAF4B HUMANPREDICTED: TAF4b UniProt NAS UniProt: Q92750 RNA polymerase II, TATA boxbinding protein (TBP)-associated factor, 105 kDa, protein from Homosapiens TB182 HUMAN 182 kDa tankyrase 1- UniProt NAS PMID: 11854288binding protein, protein from Homo sapiens TBX18 HUMAN T-boxtranscription factor UniProt NAS UniProt: O95935 TBX18, protein fromHomo sapiens TBX21 HUMAN T-box transcription factor UniProt NAS UniProt:Q9UL17 TBX21, protein from Homo sapiens TBX22 HUMAN T-box transcriptionfactor UniProt NAS UniProt: Q9Y458 TBX22, protein from Homo sapiens TBX4HUMAN T-box transcription factor UniProt NAS UniProt: P57082 TBX4,protein from Homo sapiens TCF20 HUMAN Splice Isoform 1 of UniProt NASPMID: 10995766 Transcription factor 20, protein from Homo sapiens TCFL5HUMAN TranscripTion facTor-like UniProt IDA PMID: 9763657 5 proTein,protein from Homo sapiens TCRG1 HUMAN Transcription elongation UniProtTAS PMID: 9315662 regulator 1, protein from Homo sapiens TEAD2 HUMANTranscriptional enhancer UniProt NAS PMID: 8702974 factor TEF-4, proteinfrom Homo sapiens TERA HUMAN Transitional endoplasmic UniProt IDA PMID:10855792 reticulum ATPase, protein from Homo sapiens TAS PMID: 16130169TERF1 HUMAN Splice Isoform TRF1 of UniProt NAS PMID: 9739097 Telomericrepeat binding factor 1, protein from Homo sapiens NAS PMID: 7502076TESK2 HUMAN Splice Isoform 1 of Dual UniProt ISS UniProt: Q96S53specificity testis-specific protein kinase 2, protein from Homo sapiensTF65 HUMAN Splice Isoform 1 of UniProt IDA PMID: 3140380 Transcriptionfactor p65, protein from Homo sapiens TF7L1 HUMAN Transcription factor7-like UniProt NAS PMID: 11085512 1, protein from Homo sapiens NAS PMID:1741298 TF7L2 HUMAN Splice Isoform 1 of UniProt NAS PMID: 10919662Transcription factor 7-like 2, protein from Homo sapiens TFE2 HUMANSplice Isoform E12 of UniProt NAS PMID: 2493990 Transcription factor E2-alpha, protein from Homo sapiens TFEB HUMAN Splice Isoform 1 of UniProtNAS PMID: 2115126 Transcription factor EB, protein from Homo sapiensTGIF2 HUMAN Homeobox protein UniProt TAS PMID: 11006116 TGIF2, proteinfrom Homo sapiens THB1 HUMAN Thyroid hormone receptor UniProt TAS PMID:1618799 beta-1, protein from Homo sapiens THB2 HUMAN Thyroid hormonereceptor UniProt TAS PMID: 1618799 beta-2, protein from Homo sapiensTHOC1 HUMAN THO complex subunit 1, UniProt TAS PMID: 7525595 proteinfrom Homo sapiens TIAF1 HUMAN TGFB1-induced anti- UniProt NAS PMID:9918798 apoptotic factor 1, protein from Homo sapiens TIF1A HUMAN SpliceIsoform Long of UniProt TAS PMID: 9115274 Transcription intermediaryfactor 1- alpha, protein from Homo sapiens TIF1G HUMAN Splice IsoformAlpha of UniProt NAS UniProt: Q9UPN9 Transcription intermediary factor1- gamma, protein from Homo sapiens TIM HUMAN Splice Isoform 1 ofUniProt IC PMID: 9856465 Timeless homolog, protein from Homo sapiensTIP60 HUMAN Splice Isoform 1 of UniProt TAS PMID: 8607265 Histoneacetyltransferase HTATIP, protein from Homo sapiens TITF1 HUMAN SpliceIsoform 1 of UniProt NAS UniProt: P43699 Thyroid transcription factor 1,protein from Homo sapiens TLE1 HUMAN Transducin-like enhancer UniProtTAS PMID: 1303260 protein 1, protein from Homo sapiens TLE2 HUMANTransducin-like enhancer UniProt TAS PMID: 1303260 protein 2, proteinfrom Homo sapiens TLE3 HUMAN Splice Isoform 1 of UniProt TAS PMID:1303260 Transducin-like enhancer protein 3, protein from Homo sapiensTLE4 HUMAN TLE4 protein, protein UniProt NAS PMID: 1303260 from Homosapiens TLK1 HUMAN Splice Isoform 1 of UniProt IEP PMID: 10523312Serine/threonine-protein kinase tousled-like 1, protein from Homosapiens TAS PMID: 9427565 TLK2 HUMAN Splice Isoform 1 of UniProt IEPPMID: 9427565 Serine/threonine-protein kinase tousled-like 2, proteinfrom Homo sapiens NAS PMID: 98087437 TNAP3 HUMAN Tumor necrosis factor,UniProt IDA PMID: 11463333 alpha-induced protein 3, protein from Homosapiens TNPO1 HUMAN Importin beta-2 subunit, UniProt TAS PMID: 9144189protein from Homo sapiens TNPO2 HUMAN Splice Isoform 1 of UniProt TASPMID: 9298975 Transportin-2, protein from Homo sapiens TOB2 HUMAN Tob2protein, protein UniProt TAS PMID: 10602502 from Homo sapiens TOP2AHUMAN Splice Isoform 1 of DNA UniProt TAS PMID: 6267071 topoisomerase2-alpha, protein from Homo sapiens TOP3A HUMAN Splice Isoform Long ofUniProt TAS PMID: 8622991 DNA topoisomerase III alpha, protein from Homosapiens TOP3B HUMAN Splice Isoform 1 of DNA UniProt TAS PMID: 9786843topoisomerase III beta-1, protein from Homo sapiens TOPB1 HUMAN DNAtopoisomerase II UniProt TAS PMID: 9461304 binding protein 1, proteinfrom Homo sapiens TPX2 HUMAN Targeting protein for UniProt TAS PMID:9207457 Xklp2, protein from Homo sapiens TR100 HUMAN Thyroid hormoneUniProt IDA PMID: 10235267 receptor-associated protein complex 100 kDacomponent, protein from Homo sapiens TR150 HUMAN Thyroid hormone UniProtIDA PMID: 10235267 receptor-associated protein complex 150 kDacomponent, protein from Homo sapiens TR240 HUMAN Thyroid hormone UniProtIDA PMID: 10235267 receptor-associated protein complex 240 kDacomponent, protein from Homo sapiens TR95 HUMAN Splice Isoform 1 ofUniProt NAS PMID: 10198638 Thyroid hormone receptor-associated proteincomplex 95 kDa component, protein from Homo sapiens TRA2A HUMAN SpliceIsoform Long of UniProt IDA PMID: 9546399 Transformer-2 protein homolog,protein from Homo sapiens TRA2B HUMAN Splice Isoform 1 of UniProt IDAPMID: 9546399 Arginine/serine-rich splicing factor 10, protein from Homosapiens TRABD HUMAN TRABID protein, protein UniProt IDA PMID: 11463333from Homo sapiens TRAF4 HUMAN Splice Isoform 1 of TNF UniProt TAS PMID:7592751 receptor-associated factor 4, protein from Homo sapiens TRBP2HUMAN TAR RNA-binding UniProt TAS PMID: 2011739 protein 2, protein fromHomo sapiens TREF1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 11349124Transcriptional-regulating factor 1, protein from Homo sapiens TRI22HUMAN Splice Isoform 1 of UniProt TAS PMID: 7797467 Tripartite motifprotein 22, protein from Homo sapiens TRI32 HUMAN Tripartite motifprotein UniProt TAS PMID: 7778269 32, protein from Homo sapiens TRIB3HUMAN Tribbles homolog 3, UniProt ISS UniProt: Q96RU7 protein from Homosapiens TRIP4 HUMAN Activating signal UniProt IDA PMID: 10454579cointegrator 1, protein from Homo sapiens TRP13 HUMAN Splice Isoform 1of UniProt TAS PMID: 7776974 Thyroid receptor- interacting protein 13,protein from Homo sapiens TRRAP HUMAN Splice Isoform 1 of UniProt IDAPMID: 9708738 Transformation/transcription domain-associated protein,protein from Homo sapiens TRUA HUMAN tRNA pseudouridine UniProt NASUniProt: Q9Y606 synthase A, protein from Homo sapiens TSN HUMANTranslin, protein from UniProt TAS PMID: 7663511 Homo sapiens TUB HUMANTubby protein homolog, UniProt TAS PMID: 11000483 protein from Homosapiens TULP3 HUMAN Tubby related protein 3, UniProt NAS PMID: 11375483protein from Homo sapiens TWST2 HUMAN Twist-related protein 2, UniProtIDA PMID: 11062344 protein from Homo sapiens TYDP1 HUMAN Tyrosyl-DNAUniProt NAS PMID: 10521354 phosphodiesterase 1, protein from Homosapiens U2AFL HUMAN U2 small nuclear UniProt NAS UniProt: Q15695ribonucleoprotein auxiliary factor 35 kDa subunit related-protein 1,protein from Homo sapiens U360 HUMAN Hypothetical protein UniProt NASPMID: 10873569 DKFZp586N0222, protein from Homo sapiens UB2R1 HUMANUbiquitin-conjugating UniProt NAS PMID: 8248134 enzyme E2-32 kDacomplementing, protein from Homo sapiens UB2V1 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9305758 Ubiquitin-conjugating enzyme E2 variant 1,protein from Homo sapiens UB7I1 HUMAN Splice Isoform 1 of E3 UniProt NRUniProt: Q9NWF9 ubiquitin ligase TRIAD3, protein from Homo sapiens UBIQHUMAN Ubiquitin, protein from UniProt IC PMID: 14528304 Homo sapiensUBP18 HUMAN Ubl carboxyl-terminal UniProt TAS PMID: 10777664 hydrolase18, protein from Homo sapiens UBP4 HUMAN Splice Isoform UNPEL of UniProtTAS PMID: 8183569 Ubiquitin carboxyl- terminal hydrolase 4, protein fromHomo sapiens UBP7 HUMAN Ubiquitin carboxyl- UniProt TAS PMID: 9130697terminal hydrolase 7, protein from Homo sapiens UBQL4 HUMAN Ubiquilin-4,protein from UniProt IDA PMID: 11001934 Homo sapiens UGTAP HUMAN SpliceIsoform 1 of UGA UniProt ISS UniProt: Q9HD40 suppressor tRNA- associatedprotein, protein from Homo sapiens UHMK1 HUMAN Splice Isoform 1 ofUniProt ISS UniProt: Q8TAS1 Serine/threonine-protein kinase Kist,protein from Homo sapiens UK14 HUMAN Ribonuclease UK114, UniProt TASPMID: 8530410 protein from Homo sapiens ULE1A HUMAN Ubiquitin-like1-activating UniProt NAS PMID: 10187858 enzyme E1A, protein from Homosapiens ISS UniProt: O95717 ISS UniProt: Q9P020 UNG HUMAN Splice Isoform2 of UniProt NAS PMID: 9016624 Uracil-DNA glycosylase, protein from Homosapiens USF1 HUMAN Upstream stimulatory UniProt TAS PMID: 2249772 factor1, protein from Homo sapiens UTP11 HUMAN Probable U3 small UniProt IDAPMID: 12559088 nucleolar RNA-associated protein 11, protein from Homosapiens VAV HUMAN Vav proto-oncogene, UniProt NR UniProt: P15498 proteinfrom Homo sapiens VCX1 HUMAN Variable charge X-linked UniProt IDA PMID:12826317 protein 1, protein from Homo sapiens VCX3 HUMAN Variable chargeX-linked UniProt ISS UniProt: Q9NNX9 protein 3, protein from Homosapiens VCXC HUMAN VCX-C protein, protein UniProt ISS UniProt: Q9H321from Homo sapiens VGLL1 HUMAN Transcription cofactor UniProt NAS PMID:10518497 vestigial-like protein 1, protein from Homo sapiens VHL HUMANSplice Isoform 1 of Von UniProt TAS PMID: 7604013 Hippel-Lindau diseasetumor suppressor, protein from Homo sapiens WBP11 HUMAN WWdomain-binding UniProt TAS PMID: 10593949 protein 11, protein from Homosapiens WDFY1 HUMAN WD repeat and FYVE UniProt IDA PMID: 11739631 domaincontaining protein 1, protein from Homo sapiens WDR33 HUMAN WD-repeatprotein 33, UniProt IDA PMID: 11162572 protein from Homo sapiens WDR3HUMAN WD-repeat protein 3, UniProt TAS PMID: 10395803 protein from Homosapiens WDR50 HUMAN WD-repeat protein 50, UniProt IDA PMID: 15199122protein from Homo sapiens WEE1 HUMAN Wee1-like protein kinase, UniProtTAS PMID: 8348613 protein from Homo sapiens WRB HUMAN Tryptophan-richprotein, UniProt TAS PMID: 9544840 protein from Homo sapiens WRIP1 HUMANSplice Isoform 1 of UniProt ISS UniProt: Q96S55 ATPase WRNIP1, proteinfrom Homo sapiens WRN HUMAN Werner syndrome ATP- UniProt TAS PMID:9288107 dependent helicase, protein from Homo sapiens WT1 HUMAN Wilmstumor 1 isoform UniProt NAS UniProt: Q16256 D, protein from Homo sapiensNAS UniProt: P19544 WTAP HUMAN Splice Isoform 2 of UniProt IDA PMID:10942595 Wilms' tumor 1- associating protein, protein from Homo sapiensWWTR1 HUMAN WW domain containing UniProt NAS PMID: 11118213transcription regulator protein 1, protein from Homo sapiens XAB2 HUMANXPA-binding protein 2, UniProt IC PMID: 10944529 protein from Homosapiens XPA HUMAN DNA-repair protein UniProt TAS PMID: 1601884complementing XP-A cells, protein from Homo sapiens XPO7 HUMANExportin-7, protein from UniProt IDA PMID: 11071879 Homo sapiens XRN2HUMAN 5′-3′ exoribonuclease 2, UniProt ISS UniProt: Q9H0D6 protein fromHomo sapiens YAF2 HUMAN Splice Isoform 2 of YY1- UniProt IDA PMID:11593398 associated factor 2, protein from Homo sapiens YBOX1 HUMANNuclease sensitive UniProt NAS UniProt: P67809 element binding protein1, protein from Homo sapiens YBOX2 HUMAN Y-box binding protein 2,UniProt TAS PMID: 10100484 protein from Homo sapiens YETS4 HUMAN YEATSdomain- UniProt TAS PMID: 9302258 containing protein 4, protein fromHomo sapiens YL1 HUMAN Protein YL-1, protein UniProt TAS PMID: 7702631from Homo sapiens YYY1 HUMAN Hypothetical protein, UniProt TAS PMID:8121495 protein from Homo sapiens ZBT16 HUMAN Splice Isoform PLZFB ofUniProt IDA PMID: 9294197 Zinc finger and BTB domain-containing protein16, protein from Homo sapiens ZBT38 HUMAN Zinc finger and BTB UniProtISS UniProt: Q8NAP3 domain-containing protein 38, protein from Homosapiens ZBT7A HUMAN Zinc finger and BTB UniProt ISS PMID: 15337766domain-containing protein 7A, protein from Homo sapiens ZCSL2 HUMANSplice Isoform 1 of CSL- UniProt IDA PMID: 14980502 type zinc finger-containing protein 2, protein from Homo sapiens ZEP1 HUMAN Zinc fingerprotein 40, UniProt TAS PMID: 2106471 protein from Homo sapiens ZEP2HUMAN Human immunodeficiency UniProt NAS UniProt: P31629 virus type IenHancer binding protein 2, protein from Homo sapiens ZF161 HUMAN Zincfinger protein 161 UniProt TAS PMID: 9177479 homolog, protein from Homosapiens ZFP37 HUMAN Zinc finger protein 37 UniProt NAS UniProt: Q9Y6Q3homolog, protein from Homo sapiens ZFP38 HUMAN Hypothetical proteinUniProt NAS UniProt: Q9Y5A6 DKFZp686H10254, protein from Homo sapiensZFP95 HUMAN Zinc finger protein 95 UniProt NAS PMID: 10585779 homolog,protein from Homo sapiens ZFPL1 HUMAN Splice Isoform 1 of Zinc UniProtNAS PMID: 9653652 finger protein-like 1, protein from Homo sapiens ZHANGHUMAN Host cell factor-binding UniProt IDA PMID: 15705566 transcriptionfactor Zhangfei, protein from Homo sapiens ZHX1 HUMAN Zinc fingers andUniProt IDA PMID: 12237128 homeoboxes protein 1, protein from Homosapiens ZHX2 HUMAN Zinc fingers and UniProt IDA PMID: 12741956homeoboxes protein 2, protein from Homo sapiens ZHX3 HUMAN Zinc fingersand UniProt IDA PMID: 12659632 homeoboxes protein 3, protein from Homosapiens ZIC1 HUMAN Zinc finger protein ZIC 1, UniProt IDA PMID: 8542595protein from Homo sapiens ZKSC1 HUMAN Zinc finger with KRAB UniProt NASPMID: 7557990 and SCAN domain- containing protein 1, protein from Homosapiens ZMY11 HUMAN Zinc finger MYND UniProt TAS PMID: 7621829 domaincontaining protein 11, protein from Homo sapiens ZN117 HUMAN Zinc fingerprotein 117, UniProt NAS UniProt: Q03924 protein from Homo sapiens ZN11AHUMAN Zinc finger protein 11A, UniProt NAS PMID: 8464732 protein fromHomo sapiens ZN11B HUMAN Zinc finger protein 11B, UniProt NAS UniProt:Q06732 protein from Homo sapiens ZN123 HUMAN Zinc finger protein 123,UniProt NAS PMID: 1339395 protein from Homo sapiens ZN125 HUMAN Zincfinger protein 125, UniProt NAS PMID: 1339395 protein from Homo sapiensZN126 HUMAN Zinc finger protein 126, UniProt NAS PMID: 1339395 proteinfrom Homo sapiens ZN131 HUMAN Splice Isoform 1 of Zinc UniProt NAS PMID:7557990 finger protein 131, protein from Homo sapiens ZN134 HUMAN Zincfinger protein 134, UniProt NAS PMID: 7557990 protein from Homo sapiensZN135 HUMAN Similar to Zinc finger UniProt NAS PMID: 7557990 protein135, protein from Homo sapiens ZN138 HUMAN Zinc finger protein 138,UniProt NAS PMID: 7557990 protein from Homo sapiens ZN154 HUMAN Zincfinger protein 154, UniProt NAS PMID: 7557990 protein from Homo sapiensZN165 HUMAN Zinc finger protein 165, UniProt NAS UniProt: P49910 proteinfrom Homo sapiens ZN169 HUMAN KRAB box family UniProt NAS UniProt:Q14929 protein, protein from Homo sapiens ZN184 HUMAN Zinc fingerprotein 184, UniProt NAS UniProt: Q99676 protein from Homo sapiens ZN195HUMAN Hypothetical protein UniProt NAS UniProt: O14628 DKFZp666D035,protein from Homo sapiens ZN200 HUMAN Zinc finger protein 200, UniProtNAS UniProt: P98182 protein from Homo sapiens ZN205 HUMAN Zinc fingerprotein 205, UniProt NAS UniProt: O95201 protein from Homo sapiens ZN207HUMAN Splice Isoform 1 of Zinc UniProt NAS PMID: 9799612 finger protein207, protein from Homo sapiens ZN208 HUMAN Zinc finger protein 208,UniProt NAS UNIPROT: O43345 protein from Homo sapiens ZN211 HUMAN Zincfinger protein 211 UniProt NAS UniProt: Q13398 isoform 2, protein fromHomo sapiens ZN212 HUMAN Zinc finger protein 212, UniProt NAS UniProt:Q9UDV6 protein from Homo sapiens ZN214 HUMAN Zinc finger protein 214,UniProt NAS UniProt: Q9UL59 protein from Homo sapiens ZN215 HUMAN Zincfinger protein 215, UniProt NAS UniProt: Q9UL58 protein from Homosapiens ZN219 HUMAN Zinc finger protein 219, UniProt TAS PMID: 10819330protein from Homo sapiens ZN236 HUMAN Similar to Mszf28, UniProt NASUniProt: Q9UL36 protein from Homo sapiens ZN253 HUMAN Zinc fingerprotein 253, UniProt NAS UniProt: O75346 protein from Homo sapiens ZN257HUMAN Zinc finger protein 257, UniProt NAS UniProt: Q9Y2Q1 protein fromHomo sapiens ZN265 HUMAN Splice Isoform ZIS-1 of UniProt TAS PMID:9931435 Zinc finger protein 265, protein from Homo sapiens ZN268 HUMANSplice Isoform A of Zinc UniProt NAS PMID: 11311945 finger protein 268,protein from Homo sapiens ZN277 HUMAN Zinc finger protein 277, UniProtNAS UniProt: Q9NRM2 protein from Homo sapiens ZN278 HUMAN Splice Isoform1 of Zinc UniProt TAS PMID: 10713105 finger protein 278, protein fromHomo sapiens ZN282 HUMAN Zinc finger protein 282, UniProt NAS UniProt:Q9UDV7 protein from Homo sapiens ZN297 HUMAN Zinc finger protein 297,UniProt TAS PMID: 9545376 protein from Homo sapiens ZN331 HUMAN Zincfinger protein 331, UniProt NAS UniProt: Q9NQX6 protein from Homosapiens ZN33A HUMAN Zinc finger protein 33A, UniProt NAS UniProt: Q06730protein from Homo sapiens ZN33B HUMAN Zinc finger protein 33B, UniProtNAS UniProt: Q06731 protein from Homo sapiens ZN346 HUMAN Splice Isoform1 of Zinc UniProt TAS PMID: 10488071 finger protein 346, protein fromHomo sapiens ZN37A HUMAN Zinc finger protein 37A, UniProt NAS PMID:8464732 protein from Homo sapiens ZN396 HUMAN Splice Isoform 1 of ZincUniProt IMP UniProt: Q96N95 finger protein 396, protein from Homosapiens ZN398 HUMAN Splice Isoform 1 of Zinc UniProt NAS PMID: 11779858finger protein 398, protein from Homo sapiens ZN482 HUMAN Zinc fingerprotein 482, UniProt TAS PMID: 7958847 protein from Homo sapiens ZNF19HUMAN Zinc finger protein 19, UniProt NAS PMID: 7557990 protein fromHomo sapiens ZNF22 HUMAN Zinc finger protein 22, UniProt ISS UniProt:P17026 protein from Homo sapiens ZNF24 HUMAN Zinc finger protein 24,UniProt IC PMID: 10585455 protein from Homo sapiens ZNF38 HUMAN KRAB boxfamily UniProt IC PMID: 2288909 protein, protein from Homo sapiens NASUniProt: Q9NNX8 ZNF41 HUMAN Splice Isoform 1 of Zinc UniProt NASUniProt: P51814 finger protein 41, protein from Homo sapiens ZNF69 HUMANZinc finger protein 69, UniProt NAS UniProt: Q9UC07 protein from Homosapiens ZNF70 HUMAN Zinc finger protein 70, UniProt NAS UniProt: Q9UC06protein from Homo sapiens ZNF71 HUMAN Endothelial zinc finger UniProtNAS UniProt: Q9UC09 protein induced by tumor necrosis factor alpha,protein from Homo sapiens ZNF73 HUMAN Zinc finger protein 73, UniProtNAS UniProt: O43830 protein from Homo sapiens ZNF75 HUMAN Hypotheticalprotein UniProt NAS UniProt: P51815 DKFZp667L2223, protein from Homosapiens ZNF79 HUMAN Zinc finger protein 79, UniProt NAS UniProt: Q15937protein from Homo sapiens ZNF80 HUMAN Zinc finger protein 80, UniProtNAS UniProt: P51504 protein from Homo sapiens ZNF81 HUMAN Zinc fingerprotein 81, UniProt NAS UniProt: P51508 protein from Homo sapiens ZNF83HUMAN Zinc finger protein 83, UniProt NAS UniProt: P51522 protein fromHomo sapiens ZNF84 HUMAN Zinc finger protein 84, UniProt NAS UniProt:P51523 protein from Homo sapiens ZNF85 HUMAN Zinc finger protein 85,UniProt TAS PMID: 9839802 protein from Homo sapiens ZNF8 HUMAN Zincfinger protein 8, UniProt NAS UniProt: P17098 protein from Homo sapiensZNF90 HUMAN Zinc finger protein 90, UniProt NAS UniProt: Q03938 proteinfrom Homo sapiens ZNF91 HUMAN Zinc finger protein 91, UniProt NASUniProt: Q05481 protein from Homo sapiens ZNF92 HUMAN Splice Isoform 1of Zinc UniProt NAS UniProt: Q03936 finger protein 92, protein from Homosapiens ZNF93 HUMAN Splice Isoform 1 of Zinc UniProt NAS UniProt: P35789finger protein 93, protein from Homo sapiens ZPR1 HUMAN Zinc-fingerprotein UniProt TAS PMID: 8650580 ZPR1, protein from Homo sapiens ZRF1HUMAN Zuotin-related factor 1, UniProt NAS UniProt: Q99543 protein fromHomo sapiens ZW10 HUMAN Centromere/kinetochore UniProt NAS PMID:11146660 protein zw10 homolog, protein from Homo sapiens ZWIA HUMAN ZW10interactor, UniProt IDA PMID: 8885239 antisense, protein from Homosapiens ZXDA HUMAN Zinc finger X-linked UniProt NAS UniProt: P98168protein ZXDA, protein from Homo sapiens ZXDB HUMAN Zinc finger X-linkedUniProt NAS UniProt: P98169 protein ZXDB, protein from Homo sapiens ACFHUMAN Splice Isoform 1 of UniProt IDA PMID: 10781591 APOBEC1complementation factor, protein from Homo sapiens HILS1 HUMANSpermatid-specific linker UniProt IDA PMID: 12920187 histone H1-likeprotein, protein from Homo sapiens HNRH1 HUMAN Heterogeneous nuclearUniProt TAS PMID: 7499401 ribonucleoprotein H1, protein from Homosapiens HNRH2 HUMAN Heterogeneous nuclear UniProt TAS PMID: 7499401ribonucleoprotein H′, protein from Homo sapiens HNRH3 HUMAN SpliceIsoform 1 of UniProt NAS PMID: 10858537 Heterogeneous nuclearribonucleoprotein H3, protein from Homo sapiens HNRPC HUMAN Full-lengthcDNA clone UniProt NR UniProt: P07910 CS0DA009YK08 of Neuroblastoma ofHomo sapiens, protein from Homo sapiens HNRPF HUMAN Heterogeneousnuclear UniProt TAS PMID: 7499401 ribonucleoprotein F, protein from Homosapiens HNRPG HUMAN Heterogeneous nuclear UniProt NAS PMID: 7692398ribonucleoprotein G, protein from Homo sapiens HNRPL HUMAN Heterogeneousnuclear UniProt TAS PMID: 2687284 ribonucleoprotein L isoform a, proteinfrom Homo sapiens HNRPR HUMAN Heterogeneous nuclear UniProt TAS PMID:9421497 ribonucleoprotein R, protein from Homo sapiens HNRPU HUMANSplice Isoform Long of UniProt TAS PMID: 7509195 Heterogenous nuclearribonucleoprotein U, protein from Homo sapiens HNRU2 HUMAN Heterogeneousnuclear UniProt NAS UniProt: P07029 ribonucleoprotein UP2, protein fromHomo sapiens O14979 JKTBP2, protein from UniProt TAS PMID: 9538234 Homosapiens O76022 E1B-55 kDa-associated UniProt TAS PMID: 9733834 protein,protein from Homo sapiens PTBP1 HUMAN Splice Isoform 1 of UniProt TASPMID: 1641332 Polypyrimidine tract- binding protein 1, protein from Homosapiens Q9UCE7 D(TTAGGG)N-binding UniProt TAS PMID: 8321232 protein B37= TYPE A-B heterogeneous nuclear ribonucleoprotein homolog, protein fromHomo sapiens RALY HUMAN RNA binding protein, UniProt TAS PMID: 9376072protein from Homo sapiens ROA0 HUMAN Heterogeneous nuclear UniProt TASPMID: 7585247 ribonucleoprotein A0, protein from Homo sapiens ROA1 HUMANHeterogeneous nuclear UniProt TAS PMID: 8521471 ribonucleoprotein A1isoform b, protein from Homo sapiens ROA2 HUMAN Splice Isoform B1 ofUniProt TAS PMID: 7789969 Heterogeneous nuclear ribonucleoproteinsA2/B1, protein from Homo sapiens O60934 Nibrin, protein from UniProt IDAPMID: 9590181 Homo sapiens Q63HR6 Hypothetical protein UniProt ISSUniProt: Q63HR6 DKFZp686G19151, protein from Homo sapiens RAD50 HUMANSplice Isoform 1 of DNA UniProt TAS PMID: 15279769 repair protein RAD50,protein from Homo sapiens BARX1 HUMAN Homeobox protein BarH- UniProt NASUniProt: Q9HBU1 like 1, protein from Homo sapiens GBX1 HUMAN Homeoboxprotein GBX- UniProt NAS UniProt: Q14549 1, protein from Homo sapiensHDAC8 HUMAN Splice Isoform 3 of UniProt TAS PMID: 10748112 Histonedeacetylase 8, protein from Homo sapiens HMG2 HUMAN High mobility groupUniProt TAS PMID: 1551873 protein 2, protein from Homo sapiens HXD12HUMAN Homeo box D12, protein UniProt NAS UniProt: P35452 from Homosapiens JUN HUMAN Transcription factor AP- UniProt TAS PMID: 10918580 1,protein from Homo sapiens PRRX2 HUMAN Paired mesoderm UniProt NASUniProt: Q99811 homeobox protein 2, protein from Homo sapiens SMC3 HUMANStructural maintenance of UniProt NR UniProt: Q9UQE7 chromosome 3,protein from Homo sapiens SMCE1 HUMAN Splice Isoform 1 of UniProt TASPMID: 9435219 SWI/SNF-related matrix- associated actin- dependentregulator of chromatin subfamily E member 1, protein from Homo sapiensTE2IP HUMAN Telomeric repeat binding UniProt TAS PMID: 10850490 factor 2interacting protein 1, protein from Homo sapiens ZBED1 HUMAN Zinc fingerBED domain UniProt TAS PMID: 9887332 containing protein 1, protein fromHomo sapiens ZN238 HUMAN Zinc finger protein 238, UniProt TAS PMID:9756912 protein from Homo sapiens CHK1 HUMAN Serine/threonine-proteinUniProt TAS PMID: 9382850 kinase Chk1, protein from Homo sapiens CHM1AHUMAN Splice Isoform 1 of UniProt IDA PMID: 11559747 Chargedmultivesicular body protein 1a, protein from Homo sapiens DMC1 HUMANMeiotic recombination UniProt TAS PMID: 8602360 protein DMC1/LIM15homolog, protein from Homo sapiens MCP33 HUMAN Metaphase chromosomalUniProt IDA PMID: 9543011 protein 1, protein from Homo sapiens MK67IHUMAN MKI67 FHA domain- UniProt IDA PMID: 11342549 interacting nucleolarphosphoprotein, protein from Homo sapiens NOL6 HUMAN Splice Isoform 1 ofUniProt ISS PMID: 11895476 Nucleolar protein 6, protein from Homosapiens Q8WZ42 Titin, protein from Homo UniProt ISS PMID: 9548712sapiens TAS PMID: 10481174 RCC1 HUMAN RCC1 protein, protein UniProt IDAPMID: 15014043 from Homo sapiens RGS12 HUMAN Splice Isoform 1 of UniProtTAS PMID: 10869340 Regulator of G-protein signaling 12, protein fromHomo sapiens SMC1A HUMAN Structural maintenance of UniProt TAS PMID:7757074 chromosome 1-like 1 protein, protein from Homo sapiens SUV91HUMAN Histone-lysine N- UniProt TAS PMID: 10202156 methyltransferase, H3lysine-9 specific 1, protein from Homo sapiens TBG1 HUMAN Tubulingamma-1 chain, UniProt ISS UNIPROT: P23258 protein from Homo sapiensNO55 HUMAN Nucleolar autoantigen UniProt TAS PMID: 8862517 No55, proteinfrom Homo sapiens Q6ZNA8 Hypothetical protein UniProt ISS UniProt:Q6ZNA8 FLJ16262, protein from Homo sapiens RAD51 HUMAN Splice Isoform 1of DNA UniProt ISS UniProt: Q06609 repair protein RAD51 homolog 1,protein from Homo sapiens STAG3 HUMAN Splice Isoform 1 of UniProt TASPMID: 10698974 Cohesin subunit SA-3, protein from Homo sapiens SYCP2HUMAN Synaptonemal complex UniProt NAS PMID: 10341103 protein 2, proteinfrom Homo sapiens NAS PMID: 9592139 Q6PIF2 PREDICTED: UniProt ISS PMID:15944401 hypothetical protein XP_497609, protein from Homo sapiensQ8N0S2 Conserved hypothetical UniProt ISS PMID: 15944401 protein,protein from Homo sapiens SYCP1 HUMAN Synaptonemal complex UniProt ISSPMID: 15944401 protein 1, protein from Homo sapiens NPM2 HUMANNucleoplasmin-2, protein UniProt IDA PMID: 12714744 from Homo sapiensQ8N7S8 Hypothetical protein UniProt ISS UniProt: Q8N7S8 FLJ40400,protein from Homo sapiens Q96GH7 KLHDC3 protein, protein UniProt ISSUniProt: Q96GH7 from Homo sapiens RCC1 HUMAN RCC1 protein, proteinUniProt IDA PMID: 15014043 from Homo sapiens ATRX HUMAN Splice Isoform 4of UniProt TAS PMID: 10570185 Transcriptional regulator ATRX, proteinfrom Homo sapiens CBX1 HUMAN Chromobox protein UniProt TAS PMID: 9169582homolog 1, protein from Homo sapiens CBX5 HUMAN Chromobox proteinUniProt TAS PMID: 8663349 homolog 5, protein from Homo sapiens Q9Y654Heterochromatin-specific UniProt ISS UniProt: Q9Y654 nonhistone protein,protein from Homo sapiens TB182 HUMAN 182 kDa tankyrase 1- UniProt NASPMID: 11854288 binding protein, protein from Homo sapiens H2AW HUMANCore histone macro- UniProt IDA PMID: 11331621 H2A.2, protein from Homosapiens H2AY HUMAN H2A histone family, UniProt IDA PMID: 11331621 memberY, isoform 3, protein from Homo sapiens Q96AP0 24432 protein, proteinUniProt IDA PMID: 15181449 from Homo sapiens O95268 Origin recognitionUniProt NAS PMID: 9765232 complex subunit ORC5T, protein from Homosapiens Q9NZH2 Replication initiator 1, UniProt TAS PMID: 10606657protein from Homo sapiens MCM3 HUMAN DNA replication licensing UniProtTAS PMID: 1549468 factor MCM3, protein from Homo sapiens DPOD3 HUMAN DNApolymerase delta UniProt NAS PMID: 10219083 subunit 3, protein from Homosapiens PCNA HUMAN Proliferating cell nuclear UniProt TAS PMID: 2565339antigen, protein from Homo sapiens RFC3 HUMAN Activator 1 38 kDa UniProtTAS PMID: 7774928 subunit, protein from Homo sapiens RFC4 HUMANActivator 1 37 kDa UniProt TAS PMID: 7774928 subunit, protein from Homosapiens RFC5 HUMAN Activator 1 36 kDa UniProt NAS PMID: 8999859 subunit,protein from Homo sapiens RFA1 HUMAN Replication protein A 70 kDaUniProt TAS PMID: 8756712 DNA-binding subunit, protein from Homo sapiensRFA2 HUMAN Replication protein A 32 kDa UniProt TAS PMID: 2406247subunit, protein from Homo sapiens RFA3 HUMAN Replication protein A 14kDa UniProt TAS PMID: 8454588 subunit, protein from Homo sapiens RFA4HUMAN Replication protein A 30 kDa UniProt TAS PMID: 7760808 subunit,protein from Homo sapiens CHRC1 HUMAN Chromatin accessibility UniProtNAS PMID: 10880450 complex protein 1, protein from Homo sapiens Q9P288TOK-1alpha, protein UniProt IDA PMID: 10878006 from Homo sapiens AKAP6HUMAN A-kinase anchor protein UniProt IDA PMID: 10413680 6, protein fromHomo sapiens ANX11 HUMAN Annexin A11, protein UniProt NAS PMID: 12577318from Homo sapiens ATF6A HUMAN Cyclic AMP-dependent UniProt TAS PMID:10866666 transcription factor ATF-6 alpha, protein from Homo sapiensCBX5 HUMAN Chromobox protein UniProt TAS PMID: 8663349 homolog 5,protein from Homo sapiens CENPF HUMAN CENP-F kinetochore UniProt IDAPMID: 12154071 protein, protein from Homo sapiens CLIC1 HUMAN Chlorideintracellular UniProt IDA PMID: 9139710 channel protein 1, protein fromHomo sapiens EMD HUMAN Emerin, protein from UniProt TAS PMID: 8589715Homo sapiens GNAZ HUMAN Guanine nucleotide- UniProt TAS PMID: 2117645binding protein G(z), alpha subunit, protein from Homo sapiens HAX1HUMAN HS1-associating protein UniProt TAS PMID: 9058808 X-1, proteinfrom Homo sapiens LAP2A HUMAN Lamina-associated UniProt TAS PMID:8530026 polypeptide 2 isoform alpha, protein from Homo sapiens LAP2BHUMAN ThymopoieTin isoform UniProt TAS PMID: 8530026 beTa, protein fromHomo sapiens LIS1 HUMAN Platelet-activating factor UniProt IDA PMID:11940666 acetylhydrolase IB alpha subunit, protein from Homo sapiensLY10 HUMAN Splice Isoform LYSp100- UniProt TAS PMID: 8695863 B ofNuclear body protein SP140, protein from Homo sapiens MYOF HUMAN SpliceIsoform 1 of UniProt TAS PMID: 10607832 Myoferlin, protein from Homosapiens PE2R3 HUMAN Splice Isoform EP3A of UniProt TAS PMID: 10336471Prostaglandin E2 receptor, EP3 subtype, protein from Homo sapiens PTGDSHUMAN Prostaglandin-H2 D- UniProt ISS UniProt: P41222 isomeraseprecursor, protein from Homo sapiens Q86UU5 Gametogenetin proteinUniProt ISS UniProt: Q86UU5 1a, protein from Homo sapiens Q9UN92 Nurim,protein from UniProt TAS PMID: 10402458 Homo sapiens RTN4 HUMAN SpliceIsoform 1 of UniProt IDA PMID: 11126360 Reticulon-4, protein from Homosapiens S10A6 HUMAN Calcyclin, protein from UniProt NAS PMID: 12577318Homo sapiens SRBP1 HUMAN Sterol regulatory element UniProt TAS PMID:8156598 binding transcription factor 1, isoform a, protein from Homosapiens SYNE1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 11792814Nesprin-1, protein from Homo sapiens TIP30 HUMAN Conserved hypotheticalUniProt IDA PMID: 15282309 protein, protein from Homo sapiens TREX1HUMAN Splice Isoform 1 of Three UniProt ISS UniProt: Q9Y4X2 prime repairexonuclease 1, protein from Homo sapiens ISS UniProt: Q8TEU2 NAS PMID:10391904 UN84B HUMAN Sad1/unc-84-like protein UniProt TAS PMID: 103755072, protein from Homo sapiens LMNB2 HUMAN Lamin B2, protein from UniProtNAS UniProt: Q03252 Homo sapiens Q9UHQ1 Nuclear prelamin A UniProt TASPMID: 10514485 recognition factor, protein from Homo sapiens LMNA HUMANSplice Isoform A of UniProt TAS PMID: 10080180 Lamin A/C, protein fromHomo sapiens LMNB1 HUMAN Lamin B1, protein from UniProt TAS PMID:7557986 Homo sapiens Q9BWC6 Nuclear prelamin A UniProt IDA PMID:10514485 recognition factor, isoform b, protein from Homo sapiens RM19HUMAN 39S ribosomal protein UniProt IDA PMID: 10942595 L19,mitochondrial precursor, protein from Homo sapiens SCRN1 HUMANSecernin-1, protein from UniProt IDA PMID: 10942595 Homo sapiens TAGL2HUMAN Transgelin-2, protein UniProt IDA PMID: 10942595 from Homo sapiensWTAP HUMAN Splice Isoform 2 of UniProt IDA PMID: 10942595 Wilms' tumor1- associating protein, protein from Homo sapiens AT11B HUMAN Probablephospholipid- UniProt NAS PMID: 11790799 transporting ATPase IF, proteinfrom Homo sapiens MATR3 HUMAN Matrin-3, protein from UniProt TAS PMID:2033075 Homo sapiens LBR HUMAN Lamin-B receptor, UniProt TAS PMID:8157662 protein from Homo sapiens MAN1 HUMAN Inner nuclear membraneUniProt TAS PMID: 10671519 protein Man1, protein from Homo sapiens PSN1HUMAN Splice Isoform 1 of UniProt TAS PMID: 9298903 Presenilin-1,protein from Homo sapiens PSN2 HUMAN Splice Isoform 1 of UniProt TASPMID: 9298903 Presenilin-2, protein from Homo sapiens DHCR7 HUMAN7-dehydrocholesterol UniProt IDA PMID: 9878250 reductase, protein fromHomo sapiens GUC2D HUMAN Retinal guanylyl cyclase 1 UniProt TAS PMID:7777544 precursor, protein from Homo sapiens GUC2F HUMAN Retinalguanylyl cyclase 2 UniProt TAS PMID: 7777544 precursor, protein fromHomo sapiens Q6NUM9 All-trans-13,14- UniProt ISS PMID: 15358783dihydroretinol saturase, protein from Homo sapiens RAE1L HUMANmRNA-associated protein UniProt TAS PMID: 9256445 mrnp 41, protein fromHomo sapiens colocalizes_with AAAS HUMAN Aladin, protein from UniProtIDA PMID: 12730363 Homo sapiens DD19B HUMAN Splice Isoform 1 of ATP-UniProt TAS PMID: 10428971 dependent RNA helicase DDX19B, protein fromHomo sapiens RAE1L HUMAN mRNA-associated protein UniProt TAS PMID:9256445 mrnp 41, protein from Homo sapiens TAS PMID: 10209021 IMA1 HUMANImportin alpha-1 subunit, UniProt TAS PMID: 8052633 protein from Homosapiens IMA3 HUMAN Importin alpha-3 subunit, UniProt TAS PMID: 9154134protein from Homo sapiens IMB1 HUMAN Importin beta-1 subunit, UniProtTAS PMID: 7627554 protein from Homo sapiens IMB3 HUMAN Importin beta-3,protein UniProt TAS PMID: 9271386 from Homo sapiens colocalizes_withIPO4 HUMAN Splice Isoform 1 of UniProt NAS PMID: 11823430 Importin-4,protein from Homo sapiens IPO7 HUMAN Importin-7, protein from UniProtTAS PMID: 9214382 Homo sapiens NU107 HUMAN Nuclear pore complex UniProtIDA PMID: 11564755 protein Nup107, protein from Homo sapiens IDA PMID:11684705 NU133 HUMAN Nuclear pore complex UniProt IDA PMID: 11684705protein Nup133, protein from Homo sapiens IDA PMID: 11564755 NU153 HUMANNuclear pore complex UniProt TAS PMID: 8110839 protein Nup153, proteinfrom Homo sapiens NU160 HUMAN NucleoporiN 160 kDa, UniProt IDA PMID:11564755 protein from Homo sapiens IDA PMID: 11684705 NU205 HUMANNuclear pore complex UniProt NAS PMID: 9348540 protein Nup205, proteinfrom Homo sapiens NU214 HUMAN Nuclear pore complex UniProt TAS PMID:8108440 protein Nup214, protein from Homo sapiens NUP50 HUMANNucleoporin 50 kDa, UniProt TAS PMID: 10449902 protein from Homo sapiensNUP54 HUMAN Nucleoporin 54 kDa UniProt TAS PMID: 870784 variant, proteinfrom Homo sapiens NUP62 HUMAN Nuclear pore glycoprotein UniProt IDAPMID: 1915414 p62, protein from Homo sapiens NUP88 HUMAN Nuclear porecomplex UniProt TAS PMID: 9049309 protein Nup88, protein from Homosapiens NUP98 HUMAN Splice Isoform 1 of UniProt IDA PMID: 9348540Nuclear pore complex protein Nup98-Nup96 precursor, protein from Homosapiens NAS PMID: 10087256 NUPL HUMAN Nucleoporin-like protein UniProtTAS PMID: 7637788 RIP, protein from Homo sapiens NXT1 HUMAN NTF2-relatedexport UniProt TAS PMID: 10567585 protein 1, protein from Homo sapiensO75761 Ranbp3 protein, protein UniProt NAS PMID: 9637251 from Homosapiens Q6GTM2 Nucleoporin 62 kDa, UniProt ISS UniProt: Q6GTM2 proteinfrom Homo sapiens RAE1L HUMAN mRNA-associated protein UniProt TAS PMID:9256445 mrnp 41, protein from Homo sapiens TAS PMID: 10209021 RAN HUMANGTP-binding nuclear UniProt NAS PMID: 8421051 protein RAN, protein fromHomo sapiens RBP17 HUMAN Ran-binding protein 17, UniProt NAS PMID:11024021 protein from Homo sapiens RBP23 HUMAN Ran-binding protein2-like UniProt NAS PMID: 9480752 3, protein from Homo sapiens RBP2 HUMANRan-binding protein 2, UniProt TAS PMID: 7603572 protein from Homosapiens RGP1 HUMAN Ran GTPase-activating UniProt TAS PMID: 8978815protein 1, protein from Homo sapiens RNUT1 HUMAN SNURPORTIN1, proteinUniProt TAS PMID: 9670026 from Homo sapiens SENP2 HUMAN Sentrin-specificprotease UniProt IDA PMID: 12192048 2, protein from Homo sapiens TPRHUMAN Translocated promoter UniProt TAS PMID: 7798308 region, proteinfrom Homo sapiens XPO7 HUMAN Exportin-7, protein from UniProt IDA PMID:11024021 Homo sapiens EXOS3 HUMAN Exosome complex UniProt IDA PMID:11110791 exonuclease RRP40, protein from Homo sapiens EXOS9 HUMANPolymyositis/scleroderma UniProt NAS PMID: 11879549 autoantigen 1,protein from Homo sapiens O60934 Nibrin, protein from UniProt IDA PMID:12447371 Homo sapiens Q63HR6 Hypothetical protein UniProt ISS UniProt:Q63HR6 DKFZp686G19151, protein from Homo sapiens Q9BWC6 Nuclear prelaminA UniProt IDA PMID: 10514485 recognition factor, isoform b, protein fromHomo sapiens CENPF HUMAN CENP-F kinetochore UniProt IDA PMID: 7542657protein, protein from Homo sapiens CHM1A HUMAN Splice Isoform 1 ofUniProt IDA PMID: 11559747 Charged multivesicular body protein 1a,protein from Homo sapiens DNM3A HUMAN DNA, protein from Homo UniProt ISSPMID: 12138111 sapiens ERCC8 HUMAN Splice Isoform 1 of DNA UniProt IDAPMID: 11782547 excision repair protein ERCC-8, protein from Homo sapiensMYB HUMAN Splice Isoform 1 of Myb UniProt NAS PMID: 3014652proto-oncogene protein, protein from Homo sapiens P53 HUMAN SpliceIsoform 1 of UniProt IDA PMID: 11080164 Cellular tumor antigen p53,protein from Homo sapiens PML HUMAN Splice Isoform PML-1 of UniProt TASPMID: 9294197 Probable transcription factor PML, protein from Homosapiens Q86XF5 DNA cytosine UniProt ISS PMID: 12138111 methyltransferase3 alpha, isoform a, protein from Homo sapiens Q8IZV0 DNA cytosineUniProt IDA PMID: 12138111 methyltransferase 3 alpha isoform b, proteinfrom Homo sapiens SMC3 HUMAN Structural maintenance of UniProt IDA PMID:11590136 chromosome 3, protein from Homo sapiens SMRCD HUMANSWI/SNF-related, matrix UniProt NAS PMID: 11031099 associated, actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1,protein from Homo sapiens SPTN4 HUMAN Splice Isoform 1 of UniProt IDAPMID: 11294830 Spectrin beta chain, brain 3, protein from Homo sapiensTEP1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 7876352 Telomeraseprotein component 1, protein from Homo sapiens ARSA1 HUMAN Arsenicalpump-driving UniProt TAS PMID: 9736449 ATPase, protein from Homo sapiensEXOS9 HUMAN Polymyositis/scleroderma UniProt TAS PMID: 2007859autoantigen 1, protein from Homo sapiens P53 HUMAN Splice Isoform 1 ofUniProt IDA PMID: 12080348 Cellular tumor antigen p53, protein from Homosapiens DDX21 HUMAN Splice Isoform 2 of UniProt TAS PMID: 8614622Nucleolar RNA helicase 2, protein from Homo sapiens DDX54 HUMANATP-dependent RNA UniProt ISS UniProt: Q9BRZ1 helicase DDX54, proteinfrom Homo sapiens IDA PMID: 12466272 DDX56 HUMAN Probable ATP-dependentUniProt TAS PMID: 10749921 RNA helicase DDX56, protein from Homo sapiensDEDD2 HUMAN Splice Isoform 1 of DNA- UniProt IDA PMID: 11741985 bindingdeath effector domain-containing protein 2, protein from Homo sapiensDEDD HUMAN Splice Isoform 1 of Death UniProt ISS UniProt: O75618effector domain- containing protein, protein from Homo sapiens DKC1HUMAN H/ACA ribonucleoprotein UniProt TAS PMID: 10556300 complex subunit4, protein from Homo sapiens DNJB9 HUMAN DnaJ homolog subfamily UniProtISS UniProt: Q9UBS3 B member 9, protein from Homo sapiens EXOS1 HUMAN3′-5′ exoribonuclease UniProt IDA PMID: 11812149 CSL4 homolog, proteinfrom Homo sapiens EXOS4 HUMAN Exosome complex UniProt NAS PMID: 11110791exonuclease RRP41, protein from Homo sapiens EXOS5 HUMAN Exosome complexUniProt NAS PMID: 11110791 exonuclease RRP46, protein from Homo sapiensEXOS9 HUMAN Polymyositis/scleroderma UniProt TAS PMID: 2007859autoantigen 1, protein from Homo sapiens EXOSX HUMAN Splice Isoform 1 ofUniProt TAS PMID: 1383382 Exosome component 10, protein from Homosapiens FXR1 HUMAN Fragile X mental UniProt TAS PMID: 10888599retardation syndrome- related protein 1, protein from Homo sapiens GEMI4HUMAN Component of gems 4, UniProt TAS PMID: 10725331 protein from Homosapiens GNL3 HUMAN Splice Isoform 1 of UniProt ISS UniProt: Q9BVP2Guanine nucleotide binding protein-like 3, protein from Homo sapiensIF16 HUMAN Splice Isoform 2 of UniProt IDA PMID: 14654789Gamma-interferon- inducible protein Ifi-16, protein from Homo sapiensILF2 HUMAN Interleukin enhancer- UniProt IDA PMID: 11790298 bindingfactor 2, protein from Homo sapiens IMP3 HUMAN U3 small nucleolarUniProt IDA PMID: 12655004 ribonucleoprotein protein IMP3, protein fromHomo sapiens IMP4 HUMAN U3 small nucleolar UniProt IDA PMID: 12655004ribonucleoprotein protein IMP4, protein from Homo sapiens KI67 HUMANSplice Isoform Long of UniProt NR UniProt: P46013 Antigen KI-67, proteinfrom Homo sapiens MBB1A HUMAN Splice Isoform 1 of Myb- UniProt ISSUniProt: Q9BQG0 binding protein 1A, protein from Homo sapiens MDM2 HUMANSplice Isoform Mdm2 of UniProt IDA PMID: 10707090 Ubiquitin-proteinligase E3 Mdm2, protein from Homo sapiens MK67I HUMAN MKI67 FHA domain-UniProt IDA PMID: 11342549 interacting nucleolar phosphoprotein, proteinfrom Homo sapiens MO4L2 HUMAN Mortality factor 4-like UniProt IDA PMID:10942595 protein 2, protein from Homo sapiens NEK11 HUMAN Splice Isoform1 of UniProt IDA PMID: 15161910 Serine/threonine-protein kinase Nek11,protein from Homo sapiens NHPX HUMAN NHP2-like protein 1, UniProt TASPMID: 10593953 protein from Homo sapiens NO55 HUMAN Nucleolarautoantigen UniProt TAS PMID: 8862517 No55, protein from Homo sapiensNOL1 HUMAN Proliferating-cell UniProt TAS PMID: 1394192 nucleolarantigen p120, protein from Homo sapiens NOL3 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 10196175 Nucleolar protein 3, protein from Homosapiens NOL4 HUMAN Splice Isoform 1 of UniProt TAS PMID: 9813152Nucleolar protein 4, protein from Homo sapiens NOL6 HUMAN Splice Isoform1 of UniProt ISS PMID: 11895476 Nucleolar protein 6, protein from Homosapiens NOLC1 HUMAN Nucleolar and coiled-body UniProt TAS PMID: 7657714phosphoprotein 1, protein from Homo sapiens NOP56 HUMAN Nucleolarprotein Nop56, UniProt TAS PMID: 9372940 protein from Homo sapiens NOP5HUMAN Nucleolar protein NOP5, UniProt TAS PMID: 10925205 protein fromHomo sapiens NPA1P HUMAN Nucleolar preribosomal- UniProt NAS PMID:12429849 associated protein 1, protein from Homo sapiens NPM HUMANNucleophosmin, protein UniProt IDA PMID: 12080348 from Homo sapiens NUCLHUMAN Nucleolin, protein from UniProt TAS PMID: 2394707 Homo sapiensO00366 Putative p150, protein UniProt ISS UniProt: O00366 from Homosapiens OASL HUMAN Splice Isoform p56 of 59 kDa UniProt TAS PMID:9826176 2′-5′-oligoadenylate synthetase-like protein, protein from Homosapiens P53 HUMAN Splice Isoform 1 of UniProt IDA PMID: 12080348Cellular tumor antigen p53, protein from Homo sapiens PNMA1 HUMANParaneoplastic antigen UniProt TAS PMID: 10050892 Ma1, protein from Homosapiens PTBP1 HUMAN Splice Isoform 1 of UniProt TAS PMID: 1641332Polypyrimdine tract- binding protein 1, protein from Homo sapiens Q76D35Nop132, protein from UniProt IDA PMID: 14660641 Homo sapiens Q8WYJ1 MDM2protein, protein UniProt ISS UniProt: Q8WYJ1 from Homo sapiens Q8WYJ2MDM2 protein, protein UniProt ISS UniProt: Q8WYJ2 from Homo sapiensQ96Q89 M-phase phosphoprotein UniProt IDA PMID: 11470801 1, protein fromHomo sapiens Q9H2G4 CTCL tumor antigense UniProt IDA PMID: 1139547920-4, protein from Homo sapiens Q9P1T7 HIC protein isoform p40, UniProtNAS PMID: 10671520 protein from Homo sapiens Q9UFR5 M-phasephosphoprotein UniProt ISS UniProt: Q9UFR5 1, protein from Homo sapiensRCL1 HUMAN RNA 3′-terminal UniProt NAS UniProt: Q9Y2P8 phosphatecyclase-like protein, protein from Homo sapiens DKC1 HUMAN H/ACAribonucleoprotein UniProt TAS PMID: 10556300 complex subunit 4, proteinfrom Homo sapiens IF16 HUMAN Splice Isoform 2 of UniProt IDA PMID:14654789 Gamma-interferon- inducible protein Ifi-16, protein from Homosapiens RL35 HUMAN 60S ribosomal protein UniProt TAS PMID: 2891103 L35,protein from Homo sapiens RL3 HUMAN 60S ribosomal protein UniProt TASPMID: 2891103 L3, protein from Homo sapiens RPF1 HUMAN Ribosomeproduction UniProt IDA PMID: 12429849 factor 1, protein from Homosapiens RS7 HUMAN 40S ribosomal protein S7, UniProt IDA PMID: 11823430protein from Homo sapiens S29A2 HUMAN Solute carrier family 29 UniProtTAS PMID: 7639753 (Nucleoside transporters), member 2, protein from Homosapiens SRP68 HUMAN Splice Isoform 1 of Signal UniProt TAS PMID:10618370 recognition particle 68 kDa protein, protein from Homo sapiensSUH HUMAN Splice Isoform APCR-2 of UniProt IDA PMID: 9874765 Recombiningbinding protein suppressor of hairless, protein from Homo sapiens TCOFHUMAN Treacle protein, protein UniProt IDA PMID: 15249688 from Homosapiens UBF1 HUMAN Splice Isoform UBF1 of UniProt TAS PMID: 2330041Nucleolar transcription factor 1, protein from Homo sapiens VCX1 HUMANVariable charge X-linked UniProt IEP PMID: 12826317 protein 1, proteinfrom Homo sapiens VCX3 HUMAN Variable charge X-linked UniProt ISSUniProt: Q9NNX9 protein 3, protein from Homo sapiens VCXC HUMAN VCX-Cprotein, protein UniProt ISS UniProt: Q9H321 from Homo sapiens ZN239HUMAN Zinc finger protein 239, UniProt NR UniProt: Q16600 protein fromHomo sapiens ZN274 HUMAN Splice Isoform 1 of Zinc UniProt TAS PMID:10777669 finger protein 274, protein from Homo sapiens ZN330 HUMAN Zincfinger protein 330, UniProt IDA PMID: 10593942 protein from Homo sapiensZN346 HUMAN Splice Isoform 1 of Zinc UniProt TAS PMID: 10488071 fingerprotein 346, protein from Homo sapiens ZPR1 HUMAN Zinc-finger proteinUniProt TAS PMID: 9763455 ZPR1, protein from Homo sapiens RPA1 HUMANDNA-directed RNA UniProt NAS UniProt: O95602 polymerase I largestsubunit, protein from Homo sapiens RPA5 HUMAN Splice Isoform 1 of DNA-UniProt TAS PMID: 9540830 directed RNA polymerase I 40 kDa polypeptide,protein from Homo sapiens SURF6 HUMAN Surfeit locus protein 6, UniProtISS UniProt: O75683 protein from Homo sapiens POP1 HUMAN RibonucleasesP/MRP UniProt IDA PMID: 8918471 protein subunit POP1, protein from Homosapiens POP7 HUMAN Ribonuclease P protein UniProt TAS PMID: 9630247subunit p20, protein from Homo sapiens RP30 HUMAN Ribonuclease P proteinUniProt TAS PMID: 9630247 subunit p30, protein from Homo sapiens RPP38HUMAN Ribonuclease P protein UniProt TAS PMID: 9630247 subunit p38,protein from Homo sapiens RPP40 HUMAN Ribonuclease P protein UniProt TASPMID: 9630247 subunit p40, protein from Homo sapiens BAZ2A HUMANHypothetical protein UniProt NAS PMID: 10662543 DKFZp781B109, proteinfrom Homo sapiens POP1 HUMAN Ribonucleases P/MRP UniProt IDA PMID:8918471 protein subunit POP1, protein from Homo sapiens RP29 HUMANRibonuclease P protein UniProt TAS PMID: 10352175 subunit p29, proteinfrom Homo sapiens O15446 Nucleolar fibrillar center UniProt TAS PMID:9426281 protein, protein from Homo sapiens MPP10 HUMAN U3 smallnucleolar UniProt NAS PMID: 9450966 ribonucleoprotein protein MPP10,protein from Homo sapiens NOLA2 HUMAN H/ACA ribonucleoprotein UniProtISS UniProt: Q9NX24 complex subunit 2, protein from Homo sapiens NOLA3HUMAN H/ACA ribonucleoprotein UniProt TAS PMID: 9843512 complex subunit3, protein from Homo sapiens U3IP2 HUMAN U3 small nucleolar RNA- UniProtTAS PMID: 9418896 interacting protein 2, protein from Homo sapiens 3MGHUMAN Splice Isoform 1 of DNA- UniProt TAS PMID: 108544233-methyladenine glycosylase, protein from Homo sapiens ANX11 HUMANAnnexin A11, protein UniProt NAS PMID: 12577318 from Homo sapiens ATF6AHUMAN Cyclic AMP-dependent UniProt TAS PMID: 10866666 transcriptionfactor ATF-6 alpha, protein from Homo sapiens ATX3 HUMAN Splice Isoform1 of UniProt TAS PMID: 9580663 Machado-Joseph disease protein 1, proteinfrom Homo sapiens CB80 HUMAN 80 kDa nuclear cap UniProt TAS PMID:7937105 binding protein, protein from Homo sapiens CBX1 HUMAN Chromoboxprotein UniProt TAS PMID: 9169582 homolog 1, protein from Homo sapiensCPSF3 HUMAN Cleavage and UniProt TAS PMID: 7969155 polyadenylationspecificity factor, 73 kDa subunit, protein from Homo sapiens DKC1 HUMANH/ACA ribonucleoprotein UniProt TAS PMID: 10556300 complex subunit 4,protein from Homo sapiens DPOQ HUMAN DNA polymerase theta, UniProt TASPMID: 10395804 protein from Homo sapiens FMR1 HUMAN Splice Isoform 6 ofUniProt TAS PMID: 10888599 Fragile X mental retardation 1 protein,protein from Homo sapiens FUSIP HUMAN Splice Isoform 1 of FUS- UniProtIDA PMID: 11684676 interacting serine- arginine-rich protein 1, proteinfrom Homo sapiens GIT2 HUMAN Splice Isoform 2 of ARF UniProt IDA PMID:10942595 GTPase-activating protein GIT2, protein from Homo sapiens HNRPLHUMAN Heterogeneous nuclear UniProt TAS PMID: 2687284 ribonucleoproteinL isoform a, protein from Homo sapiens HSP1 HUMAN Sperm protamine P1,UniProt TAS PMID: 2081589 protein from Homo sapiens IF16 HUMAN SpliceIsoform 2 of UniProt IDA PMID: 14654789 Gamma-interferon- inducibleprotein Ifi-16, protein from Homo sapiens IMA2 HUMAN Importin alpha-2subunit, UniProt TAS PMID: 7565597 protein from Homo sapiens ISG20 HUMANSplice Isoform 1 of UniProt TAS PMID: 9235947 Interferon-stimulated gene20 kDa protein, protein from Homo sapiens LY10 HUMAN Splice IsoformLYSp100- UniProt TAS PMID: 8695863 B of Nuclear body protein SP140,protein from Homo sapiens MCRS1 HUMAN Splice Isoform 1 of UniProt TASPMID: 9765390 Microspherule protein 1, protein from Homo sapiens MDM2HUMAN Splice Isoform Mdm2 of UniProt IDA PMID: 10707090Ubiquitin-protein ligase E3 Mdm2, protein from Homo sapiens MK67I HUMANMKI67 FHA domain- UniProt IDA PMID: 11342549 interacting nucleolarphosphoprotein, protein from Homo sapiens MRE11 HUMAN Splice Isoform 1of UniProt TAS PMID: 9651580 Double-strand break repair protein MRE11A,protein from Homo sapiens NB6M HUMAN Cell death-regulatory UniProt IDAPMID: 10924506 protein GRIM19, protein from Homo sapiens NUP54 HUMANNucleoporin 54 kDa UniProt TAS PMID: 8707840 variant, protein from Homosapiens NUP98 HUMAN Splice Isoform 1 of UniProt TAS PMID: 7736573Nuclear pore complex protein Nup98-Nup96 precursor, protein from Homosapiens OGG1 HUMAN Splice Isoform 2A of N- UniProt TAS PMID: 9223305glycosylase/DNA lyase, protein from Homo sapiens P53 HUMAN SpliceIsoform 1 of UniProt IDA PMID: 11080164 Cellular tumor antigen p53,protein from Homo sapiens IDA PMID: 12915590 PHB HUMAN Prohibitin,protein from UniProt IDA PMID: 12466959 Homo sapiens PML HUMAN SpliceIsoform PML-1 of UniProt IDA PMID: 12915590 Probable transcriptionfactor PML, protein from Homo sapiens TAS PMID: 9294197 POLH HUMANSplice Isoform 1 of DNA UniProt TAS PMID: 10385124 polymerase eta,protein from Homo sapiens POLI HUMAN DNA polymerase iota, UniProt TASPMID: 10458907 protein from Homo sapiens PPIG HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9153302 Peptidyl-prolyl cis-trans isomerase G, proteinfrom Homo sapiens PRM2 HUMAN Protamine-2, protein UniProt TAS PMID:2081589 from Homo sapiens PTBP1 HUMAN Splice Isoform 1 of UniProt TASPMID: 1641332 Polypyrimidine tract- binding protein 1, protein from Homosapiens Q8WYJ1 MDM2 protein, protein UniProt ISS UniProt: Q8WYJ1 fromHomo sapiens IDA PMID: 12915590 Q8WYJ2 MDM2 protein, protein UniProt ISSUniProt: Q8WYJ2 from Homo sapiens Q96Q89 M-phase phosphoprotein UniProtIDA PMID: 11470801 1, protein from Homo sapiens Q96SB3 Neurabin IIprotein, UniProt IMP PMID: 11278317 protein from Homo sapiens Q9UFR5M-phase phosphoprotein UniProt ISS UniProt: Q9UFR5 1, protein from Homosapiens Q9Y654 Heterochromatin-specific UniProt ISS UniProt: Q9Y654nonhistone protein, protein from Homo sapiens RECQ5 HUMAN Splice IsoformAlpha of UniProt NAS PMID: 10710432 ATP-dependent DNA helicase Q5,protein from Homo sapiens RNPC2 HUMAN Splice Isoform 2 of RNA- UniProtTAS PMID: 8227358 binding region containing protein 2, protein from Homosapiens ROA1 HUMAN Heterogeneous nuclear UniProt TAS PMID: 8521471ribonucleoprotein A1 isoform b, protein from Homo sapiens RTC1 HUMANSplice Isoform 1 of RNA UniProt TAS PMID: 9184239 3′-terminal phosphatecyclase, protein from Homo sapiens SMCA2 HUMAN Splice Isoform Long ofUniProt TAS PMID: 8670841 Possible global transcription activatorSNF2L2, protein from Homo sapiens SMCA4 HUMAN Possible global UniProtTAS PMID: 8208605 transcription activator SNF2L4, protein from Homosapiens SMCA5 HUMAN SWI/SNF-related matrix UniProt TAS PMID: 9730600associated actin dependent regulator of chromatin subfamily A member 5,protein from Homo sapiens SMRC1 HUMAN SWI/SNF-related matrix- UniProtTAS PMID: 8804307 associated actin- dependent regulator of chromatinsubfamily C member 1, protein from Homo sapiens SMRD2 HUMAN SpliceIsoform 1 of UniProt TAS PMID: 8804307 SWI/SNF-related matrix-associated actin- dependent regulator of chromatin subfamily D member 2,protein from Homo sapiens SMRD3 HUMAN Splice Isoform 1 of UniProt TASPMID: 8804307 SWI/SNF-related matrix- associated actin- dependentregulator of chromatin subfamily D member 3, protein from Homo sapiensSNF5 HUMAN Splice Isoform A of UniProt TAS PMID: 7801128 SWI/SNFrelated, matrix associated, actin dependent regulator of chromatinsubfamily B member 1, protein from Homo sapiens SRR35 HUMANOTTHUMP00000016846, UniProt ISS PMID: 11684676 protein from Homo sapiensSYMPK HUMAN Splice Isoform 1 of UniProt IDA PMID: 8769423 Symplekin,protein from Homo sapiens TDG HUMAN G/T mismatch-specific UniProt TASPMID: 9489705 thymine DNA glycosylase, protein from Homo sapiens TP53BHUMAN Tumor suppressor p53- UniProt IDA PMID: 9748285 binding protein 1,protein from Homo sapiens UNG2 HUMAN Uracil-DNA glycosylase UniProt IDAPMID: 12161446 2, protein from Homo sapiens WDHD1 HUMAN WD repeat andHMG-box UniProt TAS PMID: 9175701 DNA binding protein 1, protein fromHomo sapiens XPO1 HUMAN Exportin-1, protein from UniProt TAS PMID:9368044 Homo sapiens ZN638 HUMAN Splice Isoform 1 of Zinc UniProt TASPMID: 8647861 finger protein 638, protein from Homo sapiens ESR1 HUMANSplice Isoform Long of UniProt NAS PMID: 12351687 Estrogen receptor,protein from Homo sapiens Q9Y294 ASF1A protein, protein UniProt IDAPMID: 10759893 from Homo sapiens SMRD1 HUMAN Splice Isoform 1 of UniProtNAS PMID: 9693044 SWI/SNF-related matrix- associated actin- dependentregulator of chromatin subfamily D member 1, protein from Homo sapiensCHRC1 HUMAN Chromatin accessibility UniProt NAS PMID: 10880450 complexprotein 1, protein from Homo sapiens CAF1A HUMAN Chromatin assemblyUniProt TAS PMID: 7600578 factor 1, subunit A, protein from Homo sapiensCAF1B HUMAN Chromatin assembly UniProt TAS PMID: 7600578 factor 1subunit B, protein from Homo sapiens NP1L1 HUMAN Nucleosome assemblyUniProt TAS PMID: 8297347 protein 1-like 1, protein from Homo sapiensNP1L2 HUMAN Nucleosome assembly UniProt TAS PMID: 8789438 protein 1-like2, protein from Homo sapiens NP1L3 HUMAN Nucleosome assembly UniProt TASPMID: 8976385 protein 1-like 3, protein from Homo sapiens NP1L4 HUMANNucleosome assembly UniProt TAS PMID: 9325046 protein 1-like 4, proteinfrom Homo sapiens SIRT2 HUMAN Splice Isoform 1 of NAD- UniProt NAS PMID:12697818 dependent deacetylase sirtuin-2, protein from Homo sapiensHBXAP HUMAN Remodeling and spacing UniProt IPI PMID: 9836642 factoR 1,protein from Homo sapiens SMCA5 HUMAN SWI/SNF-related matrix UniProt IPIPMID: 9836642 associated actin dependent regulator of chromatinsubfamily A member 5, protein from Homo sapiens ACL6B HUMAN Actin-likeprotein 6B, UniProt ISS UniProt: O94805 protein from Homo sapiens ARI1AHUMAN Splice Isoform 1 of AT- UniProt ISS UniProt: O14497 richinteractive domain- containing protein 1A, protein from Homo sapiens IDAPMID: 9584200 ARI1B HUMAN Splice Isoform 1 of AT- UniProt IDA PMID:11734557 rich interactive domain- containing protein 1B, protein fromHomo sapiens NCTR1 HUMAN Splice Isoform 1 of UniProt ISS UniProt: O76036Natural cytotoxicity triggering receptor 1 precursor, protein from Homosapiens SMRC1 HUMAN SWI/SNF-related matrix- UniProt IDA PMID: 10078207associated actin- dependent regulator of chromatin subfamily C member 1,protein from Homo sapiens SMRC2 HUMAN Splice Isoform 1 of UniProt IDAPMID: 10078207 SWI/SNF-related matrix- associated actin- dependentregulator of chromatin subfamily C member 2, protein from Homo sapiensSMRD3 HUMAN Splice Isoform 1 of UniProt NAS PMID: 14701856SWI/SNF-related matrix- associated actin- dependent regulator ofchromatin subfamily D member 3, protein from Homo sapiens HCLS1 HUMANHematopoietic lineage UniProt TAS PMID: 2587259 cell-specific protein,protein from Homo sapiens MED21 HUMAN Mediator of RNA UniProt TAS PMID:8598913 polymerase II transcription subunit 21, protein from Homosapiens PRGC1 HUMAN Peroxisome proliferator- UniProt TAS PMID: 12588810activated receptor gamma coactivator 1-alpha, protein from Homo sapiensQ15161 POLR2 protein, protein UniProt NAS PMID: 3145407 from Homosapiens Q99590 SRrp129 protein, protein UniProt TAS PMID: 9224939 fromHomo sapiens RMP HUMAN RNA polymerase II UniProt TAS PMID: 9819440subunit 5-mediating protein, protein from Homo sapiens RPB11 HUMANRPB11a protein, protein UniProt TAS PMID: 8797801 from Homo sapiens RPB1HUMAN DNA-directed RNA UniProt TAS PMID: 2999107 polymerase II largestsubunit, protein from Homo sapiens RPB2 HUMAN DNA-directed RNA UniProtTAS PMID: 1518060 polymerase II 140 kDa polypeptide, protein from Homosapiens RPB3 HUMAN DNA-directed RNA UniProt NR UniProt: P19387polymerase II 33 kDa polypeptide, protein from Homo sapiens RPB4 HUMANDNA-directed RNA UniProt IC PMID: 9528765 polymerase II 16 kDapolypeptide, protein from Homo sapiens RPB5 HUMAN DNA-directed RNAUniProt TAS PMID: 7828586 polymerase II 23 kDa polypeptide, protein fromHomo sapiens RPB9 HUMAN DNA-directed RNA UniProt NR UniProt: P36954polymerase II 14.5 kDa polypeptide, protein from Homo sapiens RPC10HUMAN DNA-directed RNA UniProt NR UniProt: P53803 polymerases I, II, andIII 7.0 kDa polypeptide, protein from Homo sapiens ZN148 HUMAN Zincfinger protein 148, UniProt TAS PMID: 8355710 protein from Homo sapiensZN281 HUMAN Zinc finger protein 281, UniProt TAS PMID: 10448078 proteinfrom Homo sapiens BCL6 HUMAN B-cell lymphoma 6 UniProt NR UniProt:P41182 protein, protein from Homo sapiens CDK8 HUMAN Cell divisionprotein UniProt IDA PMID: 14638676 kinase 8, protein from Homo sapiensCRSP2 HUMAN CRSP complex subunit 2, UniProt IDA PMID: 10198638 proteinfrom Homo sapiens CRSP6 HUMAN CRSP complex subunit 6, UniProt IDA PMID:10198638 protein from Homo sapiens MED12 HUMAN Mediator of RNA UniProtIDA PMID: 10198638 polymerase II transcription subunit 12, protein fromHomo sapiens MED21 HUMAN Mediator of RNA UniProt IDA PMID: 12037571polymerase II transcription subunit 21, protein from Homo sapiens MED4HUMAN Mediator complex subunit UniProt IEP PMID: 10882111 4, proteinfrom Homo sapiens MED6 HUMAN RNA polymerase UniProt IDA PMID: 14638676transcriptional regulation mediator, subunit 6 homolog, protein fromHomo sapiens IDA PMID: 12037571 MED8 HUMAN Splice Isoform 1 of UniProtIDA PMID: 14638676 Mediator of RNA polymerase II transcription subunit 8homolog, protein from Homo sapiens PPRB HUMAN Splice Isoform 1 ofUniProt IDA PMID: 10198638 Peroxisome proliferator- activatedreceptor-binding protein, protein from Homo sapiens Q5XX09 Intersex-likeprotein, UniProt IDA PMID: 14638676 protein from Homo sapiens Q8TDE4PGC-1-related estrogen UniProt IDA PMID: 11854298 receptor alphacoactivator short isoform, protein from Homo sapiens Q96HR3TRAP/Mediator complex UniProt IDA PMID: 10198638 component TRAP25,protein from Homo sapiens Q9BUE0 MED18 protein, protein UniProt IDAPMID: 14638676 from Homo sapiens Q9P086 Similar to HSPC296, UniProt IDAPMID: 14638676 protein from Homo sapiens RBM14 HUMAN Splice Isoform 1 ofRNA- UniProt NAS PMID: 11443112 binding protein 14, protein from Homosapiens SURF5 HUMAN Splice Isoform Surf5A of UniProt IDA PMID: 14638676Surfeit locus protein 5, protein from Homo sapiens TR100 HUMAN Thyroidhormone UniProt NAS PMID: 9653119 receptor-associated protein complex100 kDa component, protein from Homo sapiens TR150 HUMAN Thyroid hormoneUniProt IDA PMID: 10198638 receptor-associated protein complex 150 kDacomponent, protein from Homo sapiens TR240 HUMAN Thyroid hormone UniProtIDA PMID: 10198638 receptor-associated protein complex 240 kDacomponent, protein from Homo sapiens TR95 HUMAN Splice Isoform 1 ofUniProt IDA PMID: 10198638 Thyroid hormone receptor-associated proteincomplex 95 kDa component, protein from Homo sapiens TRFP HUMANTRF-proximal protein UniProt NAS PMID: 9933582 homolog, protein fromHomo sapiens T2AG HUMAN Transcription initiation UniProt NAS PMID:7958900 factor IIA gamma chain, protein from Homo sapiens TF2AA HUMANTranscription initiation UniProt NR UniProt: P52655 factor IIA subunit1, protein from Homo sapiens colocalizes_with EDF1 HUMAN Splice Isoform1 of UniProt IDA PMID: 12040021 Endothelial differentiation-relatedfactor 1, protein from Homo sapiens O43604 Cofactor of initiator UniProtTAS PMID: 9418870 function, protein from Homo sapiens Q7Z7C8OTTHUMP00000016392, UniProt IDA PMID: 14580349 protein from Homo sapiensQ9BQS9 TAF3 RNA polymerase UniProt IDA PMID: 11438666 II, TATA boxbinding protein, protein from Homo sapiens RBP56 HUMAN Splice IsoformLong of UniProt NR UnitProt: Q92804 TATA-binding protein associatedfactor 2N, protein from Homo sapiens TAF10 HUMAN Transcriptioninitiation UniProt IDA PMID: 14580349 factor TFIID subunit 10, proteinfrom Homo sapiens TAF11 HUMAN Transcription initiation UniProt IDA PMID:14580349 factor TFIID subunit 11, protein from Homo sapiens TAF12 HUMANTranscription initiation UniProt IDA PMID: 14580349 factor TFIID subunit12, protein from Homo sapiens TAF13 HUMAN Transcription initiationUniProt TAS PMID: 7729427 factor TFIID subunit 13, protein from Homosapiens TAF1 HUMAN Splice Isoform 1 of UniProt TAS PMID: 7680771Transcription initiation factor TFIID subunit 1, protein from Homosapiens TAF1L HUMAN Transcription initiation UniProt ISS PMID: 12217962factor TFIID 210 kDa subunit, protein from Homo sapiens TAF4 HUMANTranscription initiation UniProt IDA PMID: 14580349 factor TFIID subunit4, protein from Homo sapiens TAF5 HUMAN Splice Isoform Long of UniProtIDA PMID: 14580349 Transcription initiation factor TFIID subunit 5,protein from Homo sapiens TAF6 HUMAN Transcription initiation UniProtIDA PMID: 14580349 factor TFIID subunit 6, protein from Homo sapiensTAF7 HUMAN Transcription initiation UniProt IDA PMID: 14580349 factorTFIID subunit 7, protein from Homo sapiens TAF9 HUMAN Transcriptioninitiation UniProt IDA PMID: 14580349 factor TFIID subunit 9, proteinfrom Homo sapiens TBP HUMAN TATA-box binding UniProt IDA PMID: 14580349protein, protein from Homo sapiens TAF6 HUMAN Transcription initiationUniProt TAS PMID: 7667268 factor TFIID subunit 6, protein from Homosapiens T2FA HUMAN Transcription initiation UniProt TAS PMID: 1734283factor IIF alpha subunit, protein from Homo sapiens ERCC2 HUMAN TFIIHbasal transcription UniProt TAS PMID: 7663514 factor complex helicasesubunit, protein from Homo sapiens ERCC3 HUMAN TFIIH basal transcriptionUniProt TAS PMID: 7663514 factor complex helicase XPB subunit, proteinfrom Homo sapiens TF2H1 HUMAN TFIIH basal transcription UniProt TASPMID: 9118947 factor complex p62 subunit, protein from Homo sapiensTF2H2 HUMAN TFIIH basal transcription UniProt NR UniProt: Q13888 factorcomplex p44 subunit, protein from Homo sapiens TF2H3 HUMAN TFIIH basaltranscription UniProt NAS UniProt: Q13889 factor complex p34 subunit,protein from Homo sapiens TF2H4 HUMAN TFIIH basal transcription UniProtTAS PMID: 9118947 factor complex p52 subunit, protein from Homo sapiensRPC10 HUMAN DNA-directed RNA UniProt NR UniProt: P53803 polymerases I,II, and III 7.0 kDa polypeptide, protein from Homo sapiens RPC11 HUMANDNA-directed RNA UniProt TAS PMID: 9869639 polymerases III 12.5 kDapolypeptide, protein from Homo sapiens RPC1 HUMAN DNA-directed RNAUniProt NAS UniProt: O14802 polymerase III largest subunit, protein fromHomo sapiens RPC62 HUMAN DNA-directed RNA UniProt TAS PMID: 9171375polymerase III 62 kDa polypeptide, protein from Homo sapiens RPC6 HUMANDNA-directed RNA UniProt NAS PMID: 10623476 polymerase III 39 kDapolypeptide, protein from Homo sapiens RPC7 HUMAN DNA-directed RNAUniProt TAS PMID: 9171375 polymerase III 32 kDa polypeptide, proteinfrom Homo sapiens RPC8 HUMAN Splice Isoform 1 of DNA- UniProt IDA PMID:12391170 directed RNA polymerase III subunit 22.9 kDa polypeptide,protein from Homo sapiens MEN1 HUMAN Splice Isoform 1 of UniProt IDAPMID: 14992727 Menin, protein from Homo sapiens NSD1 HUMAN SpliceIsoform 1 of UniProt ISS UniProt: Q96L73 Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine- 20 specific, protein fromHomo sapiens PCF11 HUMAN Pre-mRNA cleavage UniProt NAS PMID: 11060040comPlex II Protein Pcf11, protein from Homo sapiens CPSF1 HUMAN Cleavageand UniProt IDA PMID: 7590244 polyadenylation specificity factor, 160kDa subunit, protein from Homo sapiens GEMI5 HUMAN Gem-associatedprotein UniProt IDA PMID: 11714716 5, protein from Homo sapiens GEMI6HUMAN Gem-associated protein UniProt IDA PMID: 11748230 6, protein fromHomo sapiens GEMI7 HUMAN Gem-associated protein UniProt IDA PMID:12065586 7, protein from Homo sapiens HIPK2 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 14626429 Homeodomain-interacting protein kinase 2,protein from Homo sapiens Q9Y474 Zinc-finger motif- UniProt TAS PMID:9305772 enhancer binding-protein- 1, protein from Homo sapiens Q8WWY3U4/U6 snRNP-associated UniProt IDA PMID: 11867543 61 kDa protein,protein from Homo sapiens SMN HUMAN Splice Isoform SMN of UniProt NASPMID: 9845364 Survival motor neuron protein, protein from Homo sapiensNAS PMID: 8670859 U2AF1 HUMAN Splicing factor U2AF 35 kDa UniProt TASPMID: 1388271 subunit, protein from Homo sapiens Q8WWY3 U4/U6snRNP-associated UniProt IDA PMID: 11867543 61 kDa protein, protein fromHomo sapiens ZBT16 HUMAN Splice Isoform PLZFB of UniProt IDA PMID:8541544 Zinc finger and BTB domain-containing protein 16, protein fromHomo sapiens ELF4 HUMAN ETS-related transcription UniProt IDA PMID:14970218 factor Elf-4, protein from Homo sapiens HIPK3 HUMAN SpliceIsoform 1 of UniProt IDA PMID: 11034606 Homeodomain-interacting proteinkinase 3, protein from Homo sapiens ISG20 HUMAN Splice Isoform 1 ofUniProt IDA PMID: 9235947 Interferon-stimulated gene 20 kDa protein,protein from Homo sapiens colocalizes_with PML HUMAN Splice IsoformPML-1 of UniProt IDA PMID: 10910364 Probable transcription factor PML,protein from Homo sapiens TAS PMID: 9294197 not SFRS2 HUMAN Splicingfactor, UniProt IDA PMID: 15652350 arginine/serine-rich 2, protein fromHomo sapiens SP100 HUMAN Splice Isoform Sp100- UniProt TAS PMID: 9230084HMG of Nuclear autoantigen Sp-100, protein from Homo sapiens SPTN4 HUMANSplice Isoform 1 of UniProt IDA PMID: 11294830 Spectrin beta chain,brain 3, protein from Homo sapiens NXF2 HUMAN Nuclear RNA export UniProtNAS PMID: 11073998 factor 2, protein from Homo sapiens NXF3 HUMANNuclear RNA export UniProt IDA PMID: 11545741 factor 3, protein fromHomo sapiens CDK9 HUMAN Splice Isoform 1 of Cell UniProt TAS PMID:10866664 division protein kinase 9, protein from Homo sapiens ELL2 HUMANRNA polymerase II UniProt TAS PMID: 9108030 elongation factor ELL2,protein from Homo sapiens ELL3 HUMAN RNA polymerase II UniProt NAS PMID:10882741 elongation factor ELL3, protein from Homo sapiens TCEA2 HUMANTranscription elongation UniProt NAS PMID: 8566795 factor A protein 2,protein from Homo sapiens CRSP3 HUMAN Splice Isoform 1 of CRSP UniProtIDA PMID: 9989412 complex subunit 3, protein from Homo sapiens CRSP6HUMAN CRSP complex subunit 6, UniProt IDA PMID: 9989412 protein fromHomo sapiens CSP9 HUMAN Cofactor required for Sp1 UniProt IDA PMID:9989412 transcriptional activation subunit 9, protein from Homo sapiensFOXE3 HUMAN Forkhead box protein E3, UniProt IDA PMID: 10652278 proteinfrom Homo sapiens FOXF1 HUMAN Forkhead box protein F1, UniProt TAS PMID:9722567 protein from Homo sapiens FOXF2 HUMAN Forkhead box protein F2,UniProt TAS PMID: 9722567 protein from Homo sapiens HES6 HUMAN SpliceIsoform 1 of UniProt ISS PMID: 10851137 Transcription cofactor HES-6,protein from Homo sapiens KU70 HUMAN ATP-dependent DNA UniProt IDA PMID:12145306 helicase II, 70 kDa subunit, protein from Homo sapiens LMO4HUMAN LIM domain transcription UniProt ISS UniProt: P61968 factor LMO4,protein from Homo sapiens NARG1 HUMAN Splice Isoform 1 of UniProt IDAPMID: 12145306 NMDA receptor regulated protein 1, protein from Homosapiens NARGL HUMAN Splice Isoform 1 of UniProt ISS UniProt: Q6N069 NMDAreceptor regulated 1-like protein, protein from Homo sapiens NCOA6 HUMANNuclear receptor UniProt TAS PMID: 11443112 coactivator 6, protein fromHomo sapiens NKX2S HUMAN Homeobox protein Nkx- UniProt ISS UniProt:P52952 2.5, protein from Homo sapiens Q9UBQ3 Polyamine-modulated UniProtTAS PMID: 10419538 factor 1, protein from Homo sapiens Q9UKB0 Highmobility group UniProt TAS PMID: 10428834 protein-R, protein from Homosapiens Q9Y6Y0 Influenza vIrus NS1A UniProt TAS PMID: 9696811 bIndIngproteIn; NS1- bIndIng proteIn; lIkely ortholog of mouse kelch famIlyproteIn Nd1, protein from Homo sapiens RBM14 HUMAN Splice Isoform 1 ofRNA- UniProt IPI PMID: 11443112 binding protein 14, protein from Homosapiens SMAD2 HUMAN Splice Isoform Long of UniProt ISS UniProt: Q15796Mothers against decapentaplegic homolog 2, protein from Homo sapiensTCP4 HUMAN Activated RNA UniProt IDA PMID: 8062391 polymerase IItranscriptional coactivator p15, protein from Homo sapiens TF65 HUMANSplice Isoform 1 of UniProt IDA PMID: 12048232 Transcription factor p65,protein from Homo sapiens WBS14 HUMAN Splice Isoform 1 of UniProt NASPMID: 11230181 Williams-Beuren syndrome chromosome region 14 protein,protein from Homo sapiens ING2 HUMAN Inhibitor of growth UniProt IDAPMID: 15243141 protein 2, protein from Homo sapiens NFYA HUMAN SpliceIsoform Long of UniProt IDA PMID: 15243141 Nuclear transcription factorY subunit alpha, protein from Homo sapiens NFYB HUMAN Nucleartranscription UniProt IDA PMID: 15243141 factor Y subunit beta, proteinfrom Homo sapiens NFYC HUMAN Splice Isoform 3 of UniProt IDA PMID:15243141 Nuclear transcription factor Y subunit gamma, protein from Homosapiens CNOT7 HUMAN CCR4-NOT transcription UniProt NAS PMID: 9820826complex subumt 7, protein from Homo sapiens TRRAP HUMAN Splice Isoform 1of UniProt NAS PMID: 9885574 Transformation/transcriptiondomain-associated protein, protein from Homo sapiens ACL6A HUMAN SpliceIsoform 1 of Actin- UniProt IDA PMID: 10966108 like protein 6A, proteinfrom Homo sapiens ACTB HUMAN Actin, cytoplasmic 1, UniProt IDA PMID:10966108 protein from Homo sapiens RUVB1 HUMAN RuvB-like 1, protein fromUniProt IDA PMID: 10966108 Homo sapiens RUVB2 HUMAN RuvB-like 2, proteinfrom UniProt IDA PMID: 10966108 Homo sapiens TIP60 HUMAN Splice Isoform1 of UniProt IDA PMID: 10966108 Histone acetyltransferase HTATIP,protein from Homo sapiens TRRAP HUMAN Splice Isoform 1 of UniProt IDAPMID: 10966108 Transformation/transcription domain-associated protein,protein from Homo sapiens HDA10 HUMAN Splice Isoform 1 of UniProt IDAPMID: 11861901 Histone deacetylase 10, protein from Homo sapiens HDA11HUMAN Histone deacetylase 11, UniProt IDA PMID: 11948178 protein fromHomo sapiens HDAC1 HUMAN Histone deacetylase 1, UniProt TAS PMID:12711221 protein from Homo sapiens HDAC2 HUMAN Histone deacetylase 2,UniProt TAS PMID: 12711221 protein from Homo sapiens HDAC3 HUMAN SpliceIsoform 1 of UniProt TAS PMID: 12711221 Histone deacetylase 3, proteinfrom Homo sapiens HDAC4 HUMAN Histone deacetylase 4, UniProt TAS PMID:12711221 protein from Homo sapiens HDAC5 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 12711221 Histone deacetylase 5, protein from Homosapiens HDAC6 HUMAN Histone deacetylase 6, UniProt IDA PMID: 11948178protein from Homo sapiens HDAC7 HUMAN Histone deacetylase, UniProt TASPMID: 12711221 protein from Homo sapiens HDAC8 HUMAN Splice Isoform 3 ofUniProt TAS PMID: 12711221 Histone deacetylase 8, protein from Homosapiens HDAC9 HUMAN Splice Isoform 1 of UniProt TAS PMID: 12711221Histone deacetylase 9, protein from Homo sapiens MTA2 HUMANMetastasis-associated UniProt TAS PMID: 10444591 protein MTA2, proteinfrom Homo sapiens SAP18 HUMAN Sin3 associated UniProt TAS PMID: 9150135polypeptide p18, protein from Homo sapiens SAP30 HUMAN Histonedeacetylase UniProt TAS PMID: 9651585 complex subunit SAP30, proteinfrom Homo sapiens TAF6L HUMAN TAF6-like RNA UniProt TAS PMID: 9674425polymerase II p300/CBP- associated factor- associated factor 65 kDasubunit 6L, protein from Homo sapiens colocalizes_with DP13A HUMANDCC-interacting protein UniProt IDA PMID: 15016378 13 alpha, proteinfrom Homo sapiens colocalizes_with DP13B HUMAN DCC-interacting proteinUniProt IDA PMID: 15016378 13 beta, protein from Homo sapiens P66A HUMANSplice Isoform 1 of UniProt IDA PMID: 12183469 Transcriptional repressorp66 alpha, protein from Homo sapiens ISS UniProt: Q96F28 SDS3 HUMAN Sin3histone deacetylase UniProt ISS PMID: 11909966 corepressor complexcomponent SDS3, protein from Homo sapiens Q16219 Insulin activatorfactor, UniProt NAS PMID: 7935390 protein from Homo sapiens TF3B HUMANSplice Isoform 1 of UniProt NAS PMID: 20380946 Transcription factor IIIB90 kDa subunit, protein from Homo sapiens NAS PMID: 8943358 TF3C1 HUMANSplice Isoform 1 of UniProt NR UniProt: Q12789 General transcriptionfactor 3C polypeptide 1, protein from Homo sapiens TF3C2 HUMAN G-proteinbeta WD-40 UniProt NR UniProt: Q8WUA4 repeat containing protein, proteinfrom Homo sapiens TF3C3 HUMAN Splice Isoform 1 of UniProt TAS PMID:10373544 General transcription factor 3C polypeptide 3, protein fromHomo sapiens TF3C4 HUMAN General transcription UniProt TAS PMID:10523658 factor 3C polypeptide 4, protein from Homo sapiens TF3C5 HUMANSplice Isoform 1 of UniProt TAS PMID: 10373544 General transcriptionfactor 3C polypeptide 5, protein from Homo sapiens ARI4A HUMAN SpliceIsoform I of AT- UniProt IPI PMID: 12724404 rich interactive domain-containing protein 4A, protein from Homo sapiens IDA PMID: 11283269JAZF1 HUMAN Splice Isoform 1 of UniProt IDA PMID: 15302918 Juxtaposedwith another zinc finger protein 1, protein from Homo sapiens PHF12HUMAN Splice Isoform 2 of PHD UniProt IDA PMID: 11390640 finger protein12, protein from Homo sapiens Q9HAQ4 Zinc finger protein 350, UniProtIDA PMID: 11090615 protein from Homo sapiens RNF12 HUMAN RING fingerprotein 12, UniProt NAS PMID: 11013082 protein from Homo sapiens SMCE1HUMAN Splice Isoform 1 of UniProt IPI PMID: 12192000 SWI/SNF-relatedmatrix- associated actin- dependent regulator of chromatin subfamily Emember 1, protein from Homo sapiens colocalizes_with SMRC2 HUMAN SpliceIsoform 1 of UniProt IPI PMID: 12192000 SWI/SNF-related matrix-associated actin- dependent regulator of chromatin subfamily C member 2,protein from Homo sapiens ZBT16 HUMAN Splice Isoform PLZFB of UniProtIDA PMID: 12802276 Zinc finger and BTB domain-containing protein 16,protein from Homo sapiens DPOLZ HUMAN DNA polymerase zeta UniProt NRUNIPROT: O60673 catalytic subunit, protein from Homo sapiens ANC4 HUMANSplice Isoform 1 of UniProt TAS PMID: 9469815 Anaphase promoting complexsubunit 4, protein from Homo sapiens ANC5 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9469815 Anaphase promoting complex subunit 5, proteinfrom Homo sapiens APC10 HUMAN Anaphase promoting UniProt NAS PMID:10318877 complex subunit 10, protein from Homo sapiens APC11 HUMANSplice Isoform 1 of UniProt IDA PMID: 11739784 Anaphase promotingcomplex subunit 11, protein from Homo sapiens APC7 HUMAN Anaphasepromoting UniProt NR UniProt: Q9UJX3 complex subunit 7, protein fromHomo sapiens BUB1B HUMAN Mitotic checkpoint UniProt TAS PMID: 10477750serine/threonine-protein kinase BUB1 beta, protein from Homo sapiensCDC23 HUMAN Splice Isoform 1 of Cell UniProt IDA PMID: 14657031 divisioncycle protein 23 homolog, protein from Homo sapiens CDC27 HUMAN ProteinCDC27Hs, UniProt NR UniProt: P30260 protein from Homo sapiens CUL7 HUMANCullin-7, protein from UniProt NAS PMID: 12481031 Homo sapiens FZR HUMANSplice Isoform 1 of Fizzy- UniProt TAS PMID: 9734353 related proteinhomolog, protein from Homo sapiens Q8NHZ8 CDC26 subunit of UniProt IDAPMID: 10922056 anaphase promoting complex, protein from Homo sapiensBARD1 HUMAN BRCA1-associated RING UniProt IDA PMID: 15265711 domainprotein 1, protein from Homo sapiens BRCA1 HUMAN Breast cancer type 1UniProt IDA PMID: 15265711 susceptibility protein, protein from Homosapiens ERCC1 HUMAN DNA excision repair UniProt IDA PMID: 3290851protein ERCC-1, protein from Homo sapiens ERCC4 HUMAN Excision rEpaircross- UniProt IDA PMID: 10644440 complEmEnting rodEntr EpairdEficiEncy, complEmEntation group 4, protein from Homo sapiens ERCC8HUMAN Splice Isoform 1 of DNA UniProt IDA PMID: 12732143 excision repairprotein ERCC-8, protein from Homo sapiens CSN2 HUMAN Splice Isoform 1 ofCOP9 UniProt IDA PMID: 9535219 signalosome complex subunit 2, proteinfrom Homo sapiens GEMI4 HUMAN Component of gems 4, UniProt TAS PMID:10725331 protein from Homo sapiens LSM6 HUMAN U6 snRNA-associatedUniProt TAS PMID: 10523320 Sm-like protein LSm6, protein from Homosapiens RSMB HUMAN Splice Isoform SM-B′ of UniProt TAS PMID: 2531083Small nuclear ribonucleoprotein associated proteins B and B′, proteinfrom Homo sapiens RUXE HUMAN Small nuclear UniProt NAS PMID: 2974536ribonucleoprotein E, protein from Homo sapiens RSMB HUMAN Splice IsoformSM-B′ of UniProt TAS PMID: 2531083 Small nuclear ribonucleoproteinassociated proteins B and B′, protein from Homo sapiens RUXE HUMAN Smallnuclear UniProt NAS PMID: 2974536 ribonucleoprotein E, protein from Homosapiens RUXG HUMAN Small nuclear UniProt NAS PMID: 7744013ribonucleoprotein G, protein from Homo sapiens SF3A2 HUMAN Splicingfactor 3A subunit UniProt TAS PMID: 8211113 2, protein from Homo sapiensSF3B3 HUMAN Splicing factor 3B subunit UniProt TAS PMID: 10490618 3,protein from Homo sapiens U3IP2 HUMAN U3 small nucleolar RNA- UniProtTAS PMID: 9418896 interacting protein 2, protein from Homo sapiens RU1CHUMAN U1 small nuclear UniProt TAS PMID: 2971157 ribonucleoprotein C,protein from Homo sapiens SNRPA HUMAN U1 small nuclear UniProt NRUniProt: P09012 ribonucleoprotein A, protein from Homo sapiens PHF5AHUMAN PHD finger-like domain UniProt IDA PMID: 12234937 protein 5A,protein from Homo sapiens RU2A HUMAN U2 small nuclear UniProt TAS PMID:2928112 ribonucleoprotein A′, protein from Homo sapiens RU2B HUMAN U2small nuclear UniProt TAS PMID: 2951739 ribonucleoprotein B″, proteinfrom Homo sapiens LSM4 HUMAN U6 snRNA-associated UniProt TAS PMID:10369684 Sm-like protein LSm4, protein from Homo sapiens Q8WWY3 U4/U6snRNP-associated UniProt IDA PMID: 11867543 61 kDa protein, protein fromHomo sapiens API5 HUMAN Splice Isoform 1 of UniProt ISS PMID: 11555636Apoptosis inhibitor 5, protein from Homo sapiens BCAS2 HUMAN Breastcarcinoma UniProt IDA PMID: 12169396 amplified sequence 2, protein fromHomo sapiens DHX8 HUMAN ATP-dependent RNA UniProt TAS PMID: 7935475helicase DHX8, protein from Homo sapiens GEMI2 HUMAN Splice Isoform 1 ofUniProt TAS PMID: 9323129 Survival of motor neuron protein-interactingprotein 1, protein from Homo sapiens PPIH HUMAN Peptidyl-prolylcis-trans UniProt TAS PMID: 9570313 isomerase H, protein from Homosapiens PRP17 HUMAN Pre-mRNA splicing factor UniProt TAS PMID: 9524131PRP17, protein from Homo sapiens PRP18 HUMAN Splice Isoform 1 of Pre-UniProt TAS PMID: 9000057 mRNA splicing factor 18, protein from Homosapiens PRP4 HUMAN Splice Isoform 1 of UniProt NAS PMID: 9328476 U4/U6small nuclear ribonucleoprotein Prp4, protein from Homo sapiens PRPF3HUMAN Splice Isoform 1 of UniProt NAS PMID: 9328476 U4/U6 small nuclearribonucleoprotein Prp3, protein from Homo sapiens PRPU HUMAN U5snRNP-associated 102 kDa UniProt NAS PMID: 10788320 protein, proteinfrom Homo sapiens Q9Y6Y0 Influenza vIrus NS1A UniProt TAS PMID: 9696811bIndIng proteIn; NS1- bIndIng proteIn; lIkely ortholog of mouse kelchfamIly proteIn Nd1, protein from Homo sapiens RSMB HUMAN Splice IsoformSM-B′ of UniProt TAS PMID: 2531083 Small nuclear ribonucleoproteinassociated proteins B and B′, protein from Homo sapiens RUXE HUMAN Smallnuclear UniProt NAS PMID: 2974536 ribonucleoprotein E, protein from Homosapiens RUXG HUMAN Small nuclear UniProt TAS PMID: 7744013ribonucleoprotein G, protein from Homo sapiens SF3A2 HUMAN Splicingfactor 3A subunit UniProt TAS PMID: 8211113 2, protein from Homo sapiensSF3A3 HUMAN Splicing factor 3A subunit UniProt TAS PMID: 8022796 3,protein from Homo sapiens SF3B1 HUMAN Splicing factor 3B subunit UniProtNAS PMID: 9585501 1, protein from Homo sapiens SF3B2 HUMAN Splicingfactor 3B Subunit UniProt TAS PMID: 8566756 2, protein from Homo sapiensSF3B3 HUMAN Splicing factor 3B subunit UniProt TAS PMID: 10490618 3,protein from Homo sapiens SF3B4 HUMAN Splicing factor 3B subunit UniProtTAS PMID: 7958871 4, protein from Homo sapiens SNW1 HUMAN Nuclearprotein Skip, UniProt IDA PMID: 15194481 protein from Homo sapiens SPF30HUMAN Survival of motor neuron- UniProt TAS PMID: 9731529 relatedsplicing factor 30, protein from Homo sapiens TXN4A HUMANThioredoxin-like protein UniProt TAS PMID: 10610776 4A, protein fromHomo sapiens U520 HUMAN U5 small nuclear UniProt IDA PMID: 8670905ribonucleoprotein 200 kDa helicase, protein from Homo sapiens U5S1 HUMAN116 kDa U5 small nuclear UniProt TAS PMID: 9233818 ribonucleoproteincomponent, protein from Homo sapiens DKC1 HUMAN H/ACA ribonucleoproteinUniProt IDA PMID: 12135483 complex subunit 4, protein from Homo sapiensTEBP HUMAN Telomerase-binding UniProt IDA PMID: 12135483 protein p23,protein from Homo sapiens TEP1 HUMAN Splice Isoform 1 of UniProt IDAPMID: 12135483 Telomerase protein component 1, protein from Homo sapiensTERT HUMAN Telomerase reverse UniProt IDA PMID: 12135483 transcriptase,protein from Homo sapiens

TABLE 2 Proteins With a Known Function in Splicing and RNA ProcessingAcc. no.a Name Comments snRNP core proteins SWISS-PROT: Q15357a Sm GSWISS-PROT: Q15356 Sm F SWISS-PROT: P08578 Sm E SWISS-PROT: P13641 Sm D1SWISS-PROT: P43330 Sm D2 SWISS-PROT: P43331 Sm D3 SWISS-PROT: P14678 SmB/B′ Ut snRNP SWISS-PROT: P09234 U1 snRNP C SWISS-PROT: P09012 U1 snRNPA SWISS-PROT: P08621 U1 snRNP 70 kDa U2 snRNP SWISS-PROT: Q15427 SAP 49SWISS-PROT: Q12874 SAP 61 SWISS-PROT: Q15428 SAP 62 SWISS-PROT: Q15459SAP 114 SWISS-PROT: Q15393 SAP 130 SWISS-PROT: Q13435 SAP 145SWISS-PROT: 075533 SAP 155 SWISS-PROT: Q01081 U2AF 35 kDa SWISS-PROT:P26368 U2AF 65 kDa SWISS-PROT: P09661 U2 snRNP A′ SWISS-PROT: P08579 U2snRNP B″ US snRNP ENSP00000263694, U5 snRNP 40 kDa Q96D17ENSP00000261905, U5 snRNP 100 kDa Q9BUQ8 ENSP00000266079, U5 snRNP 102kDa O94906 SWISS-PROT: Q15029 U5 snRNP 116 kDa SWISS-PROT: 075643 U5snRNP 200 kDa ENSP00000254706, U5 snRNP 220 kDa Q6P2Q9 U6 snRNPSWISS-PROT: Q9Y333 LSm2 SWISS-PROT: Q9Y4Z1 LSm3 SWISS-PROT: Q9Y4Z0 LSm4SWISS-PROT: Q9Y4Y8 LSm6 SWISS-PROT: Q9UK45 LSm7 SWISS-PROT: O95777 LSm8U4/U6 snRNP ENSP00000259401 U4/U6 snRNP hPrp4 ENSP00000236015, U4/U6snRNP hPrp3 O4339S ENSP00000291763 U4/U6 snRNP 61 kDa U4/U6.U5 snRNPSWISS-PROT: P55769 U4/U6.snRNP 15.5 kDa ENSP00000263858 U4/U6.U5 snRNP65 kDa ENSP00000256313 SART-1 = U4/U6.U5 snRNP 110 kDa SR proteinsSWISS-PROT: Q07955 SF2 SWISS-PROT: Q16629 9G8 SWISS-PROT: Q01130 SC35SWISS-PROT: P23152 SRp20 SWISS-PROT: Q13242 SRp30C SWISS-PROT: Q05519SRp54 SWISS-PROT: Q13247 SRp55 TREMBL: Q8WXA9 Splicing factor,arginine/serine- rich 12 ENSP00000255590 Ser/Arg-related nuclear matrixprotein Other splicing factors ENSP00000227503 SF1 ENSP00000235397 SPF27ENSP00000239010 SPF30 ENSP00000263697 SPF31 TREMBL: O75939; SPF45 Q96GY6ENSP00000265414 CDC5-related protein SWISS-PROT: Q13573 SKIP TREMBL:Q9NZA0 PUF60 TREMBL: O43660 Pleiotropic regulator 1 ENSP00000253363CC1.3 ENSP00000296702 CA150 SWISS-PROT: Q14562 DEAH-box protein 8SWISS-PROT: O43143 DEAD/H-box-15 SWISS-PROT: O60231 DEAD/H-box-16ENSP00000268482 hPRP16 SWISS-PROT: O60508 hPRP17 ENSP00000198939 ERPROT213-21 (+N- (+ENSP00000248044) terminal extension of ERPROT)ENSP00000290341 IGE-II mRNA-binding protein 1 SWISS-PROT: P23246PTB-associated splicing factor ENSP00000266611 IK factor ENSP00000257528SLU7 ENSP00000216727 poly(A)-binding protein II ENSP00000293531 KH-typesplicing regulatory protein ENSP00000294623 far upstream element-bindingprotein 1 ENSP00000227524 nuclear matrix protein NMP200 TREMBL: Q96HB0HCNP protein ENSP00000278799 crooked neck-like 1 SWISS-PROT: Q9Y3B4pre-mRNA branch site protein p14 ENSP00000292123 scaffold attachmentfactor B ENSP00000261167 SH3 domain-binding protein SNP70 hnRNPENSP00000257767 GRY-RBP SWISS-PROT: Q13151 hnRNP A0 SWISS-PROT: P09651hnRNP A1 SWISS-PROT: P22626 hnRNP A2/hnRNP B1 ENSP00000298069 hnRNP A3ENSP00000261952 hnRNP AB, isoform a SWISS-PROT: P07910 hnRNP CSWISS-PROT: Q14103 hnRNP D ENSP00000295469 hnRNP D-like SWISS-PROT:P52597 hnRNP F SWISS-PROT: P38159 hnRNP G SWISS-PROT: P31943 hnRNP HENSP00000265866 hnRNP H3 SWISS-PROT: P26599 Polypyrimidine tract-bindingprotein; hnRNP I ENSP00000297818 hnRNP K SWISS-PROT: P14866 hnRNP LSWISS-PROT: P52272 hnRNP M SWISS-PROT: O43390 hnRNP R Q00839 hnRNP UTREMBL: O76022 E1B-55kDa-associated protein 5 RNA processing SWISS-PROT:P52298 CBP 20 kDa SWISS-PROT: Q09161 CBP 80 kDa SWISS-PROT: P17844DEAD/H-box-5; RNA helicase p68 SWISS-PROT: P35637 RNA-binding proteinFUS SWISS-PROT: Q01844 RNA-binding protein EWS SWISS-PROT: Q12906Interleukin enhancer- binding factor 3 ENSP00000270794 TLS-associatedserine- arginine protein 2 RNA processing ENSP00000269407 AlySWISS-PROT: Q9UBU9 Tap ENSP00000261600 hHpr1 SWISS-PROT: Q08211 RNAhelicase A ENSP00000264073 ELAV-like protein 1 (Hu- antigen R)SWISS-PROT: P43243 matrin 3 SWISS-PROT: P55265 Double-stranded RNA-specific adenosine deaminase (DRADA) ENSP00000300291 CPSF 25 kDaENSP00000292476 CPSF 30 kDa ENSP00000266679 similar to CPSF 68 kDaSWISS-PROT: Q9UKF6 CPSF 73 kDa SWISS-PROT: Q9P2I0 CPSF 100 kDaSWISS-PROT: Q10570 CPSF 160 kDa ENSP00000227158 cleavage stimulationfactor subunit 3 SWISS-PROT: P05455 Lupus La protein: Sjogren syndrometype B antigen SWISS-PROT: Q06265 Polymyositis/scleroderma autoantigen 1SWISS-PROT: Q01780 Polymyositis/scleroderma autoantigen 2 SWISS-PROT:Q9Y2L1 Exosome complex exonuclease RRP44 SWISS-PROT: Q9NPD3 Exosomecomplex exonuclease RRP41 ENSP00000262489 Dhm1-like protein a SWISS-PROTor ENSEMBL accession numbers are given at http://srs.embl-heidelberg.de:8000/srs5/ and http://www.ensembl.org. Novel ProteinsNovel proteins and proteins with unclear functions with sequencesimilarities implicating them in splicing/mRNA processingENSP00000295270 Hypothetical protein Similar to U5 snRNP 200 kDaENSP00000272417 CDNA FLJ13778 fis Similar to U5 snRNP 200 kDaENSP00000301345 Hypothetical protein Similar to U5 snRNP 220 kDa TREMBL:Q9NUY0 CDNA FLJ11063 fis Similar to arginine/serine-rich 4 SWISS-PROT:Q13523 Serine/threonine-protein kinase Ser/Thr protein kinase family,similar to S. pombe PRP4 ENSP00000296630 Hypothetical protein RRMdomain, bipartite NLS, similar to arginine/serine-rich 11ENSP00000266057 CDNA FLJ10998 fis Similar to RNA lariat debranchingenzyme ENSP00000273541 Hypothetical protein Similar to Isy ip, apotential splice factor in yeast XP_013029 Hypothetical protein Similarto U2 snRNP A′ ENSP00000286032 Hypothetical protein Similar to hnRNP A3ENSP00000301786 Hypothetical protein Similar to hnRNP U ENSP000000301784Hypothetical protein Similar to hnRNP U ENSP00000261832 Hypotheticalprotein BASIC, basic domain DKFZp434E2220 in HLH proteins of MYODfamily, PSP, proline-rich domain in spliceo- some-associated proteins,zinc finger CCHC, zinc knuckle ENSP00000244367 CGI- 124 proteinCyclophilin-type peptidyl-prolyl cis-trans isomerase ENSP00000215824CYP-60 Cyclophilin-type peptidyl-prolyl cis-trans isomeraseENSP00000234288 PPIL3b Cyclophilin-type peptidyl-prolyl cis-transisomerase ENSP00000282972 Serologically defined Cyclophilin-typepeptidyl-prolyl colon cancer antigen 10 cis-trans isomerase bipartiteNLS SWISS-PROT: Q9UNP9 Cyclophilin E Cyclophilin-type peptidyl-prolylcis-trans isomerase RRM domain ENSP00000261308 KIAA0073 proteinCyclophilin-type peptidyl-prolyl cis-trans isomerase G-protein betaWD-40 repeats SWISS-PROT: Q92841 Probable RNA-dependent DEAD/DEAH-boxhelicase helicase p72 ENSP00000274514 RNA helicase DEAD/DEAH-boxhelicase ENSP00000242776 Hypothetical protein Similar to nuclear RNAhelicase, DECD variant of DEAD-box helicase family SWISS-PROT: Q92499DDX1 DEAD/DEAH-box helicase, SPRY domain SWISS-PROT: Q9NR30 DDX21DEAD/DEAH-box helicase, bipartite NLS SWISS-PROT: Q9UJV9 DEAD-boxprotein DEAD/DEAH-box abstract homolog helicase, zinc finger CCHC typeENSP00000218971 DDX26 DEAD-box, von Willebrand factor type A domainSWISS-PROT: P38919 Eukaryotic initiation DEAD-box helicase factor4A-like NUK-34 ENSP00000297920 Hypothetical protein Double-strandedFLJ11307 RNA-binding domain (DsRBD) ENSP00000263115 Hypothetical proteinG-patch domain ENSP00000277477 Far upstream element KH domain (FUSE)binding protein 3 ENSP00000295749 KIAA 1604 protein MIF4G, middle domainof eukaryotic initiation factor 4G and MA3 domain, bipartite NLSENSP00000298643 PRO1777 PWI domain SWISS-PROT: Q9Y580 RNA-bindingprotein 7 RRM domain SWISS-PROT: O43251 RNA-binding protein 9 RRM domainENSP00000295971 Hypothetical protein RRM domain FLJ20273 ENSP00000266301KIAA 1649 protein RRM domain SWISS-PROT: Q9Y388 Hypothetical protein RRMdomain CGI-79.B SWISS-PROT: Q02040 B-lymphocyte antigen RRM domainprecursor ENSP00000262632 Hypothetical 47.4 kDa RRM domain,ATP/GTP-binding site motif A (P-loop) ENSP00000293677 Hypotheticalprotein RRM domain, Bipartite NLS SWISS-PROT: Q9BXP5 Arsenite-resistanceprotein 2 RRM domain, Bipartite NLS ENSP00000220496 Hypothetical proteinRRM domain, DNAJ heat shock FLJ10634 protein, bipartite NLS TREMBL:O00425 Putative RNA-binding protein RRM domain, KH domain KOCENSP00000262710 KIAA0670 protein RRM domain, SAP domain TREMBL: Q96SC6OTT-MAL RRM domain, SAP domain ENSP00000295996 K1AA0332 protein RRMdomain, Surp domain Bipartite NLS ENSP00000199814 Hypothetical proteinRRM domain, Zinc FLJ10290 finger C-x8-C-x5-C-x3-H type SWISS-PROT:P98175 RNA-binding protein 10 RRM domain, C2H2 type zinc finger,bipartite NLS ENSP00000261972 Hypothetical protein S164 RRM domain, PWIdomain, bipartite (+ENSP00000261973) (+N-terminal extension: CDNA: NLS,Spectrin repeat FLJ22454 fis, clone HRC09703) (ENSP00000261973 encodesthe N-terminal extension of ENSP00000261972) TREMBL: Q9UQ35 RNA-bindingprotein RS domain ENSP00000247001 F23858_1 Surp domain, G-patch domainENSP00000299951 Hypothetical protein U1-like zinc finger, bipartite NLSENSP00000281372 HsKin17 protein C2H2 zinc finger TREMBL: Q96KR1 PutativeZinc finger protein C2H2 zinc finger ENSP00000239893 OPA-interactingprotein OIP2 3′ exoribonuclease family Novel proteins withoutsimilarities implicating them in splicing/mRNA processing SWISS-PROT:Q9C0J8 WDC146 G-protein beta WD-40 repeats ENSP00000253952 Hypothetical34.8 kDa protein G-protein beta WD-40 repeats ENSP00000263222Hypothetical 57.5 kDa protein G-protein beta WD-40 repeatsENSP00000156471 K1AA0560 protein ATP/GTP-binding site motif A (P-loop)SWISS-PROT: Q9UH06 Hypothetical 12.4 kDa protein PHD-finger (C4HC3 zincfinger) ENSP00000216252 BK223H9 belongs to the UPFO123 family ofhypothetical proteins ENSP00000260210 Hypothetical protein MGC13125Bipartite NLS, ankyrin similarity ENSP00000257181 Hypothetical proteinFLJ14936 Bipartite NLS, similar to unknowns ENSP00000290008 Hypotheticalprotein Bipartite NLS SWISS-PROT: Q9NZB2 C9orf10 protein Bipartite NLS,similar to unknowns ENSP00000247026 Hypothetical 66.4 kDa proteinBipartite NLS ENSP00000236273 GCIP-interacting protein p29 BipartiteNLS, similar to unknowns ENSP00000292314 Hypothetical protein BipartiteNLS, similar to unknowns ENSP00000266923 C21orf70 Bipartite NLS, similarto unknowns NSP00000221899 NY-REN-24 antigen Bipartite NLS,Ezrin/radixin/moesin family; similar to Drosophila cactin SWISS-PROT:Q14331 FRG1 protein (FSHD region gene Bipartite NLS, 1 protein)Lipocalin-related protein and Bos/Can/Equ allergen domain SWISS-PROT:P42285 KIAA0052 protein SKI2 helicase family ENSP00000221413 CGI-46protein DnaB helicase family ENSP00000222969 G10 protein homolog (EDG-2)G10 protein family ENSP00000279839 Adrenal gland protein AD-002GTP-binding signal recognition particle (SRP54) G-domain ENSP00000278702Similar to nuclear mitotic Involucrin repeat, G-protein gamma apparatusprotein 1 subunit, DNA gyrase/topoisomerase IV, subunit A, M proteinrepeat, bZIP (Basic-leucine zipper) transcription factor family SWISS-PROT: Q92733 Proline-rich protein PRCC Proline-rich extensionENSP00000263905 KIAA1461 protein PWWP domain, Methyl-CpG binding domainXP_089514 Hypothetical protein Similar to nucleophosmin ENSP00000258457Hypothetical 25.9 kDa protein Similar to Xenopus ashwin TREMBL: Q8WYA6Nuclear associated protein Similar to Bos taurus P14 TREMBL: Q13769Hypothetical protein Similarity to intermediate filament b [Dugesiajaponica] SWISS-PROT: Q9Y5B6 GC-rich sequence DNA-binding Similar toC-TERMINAL OF factor homolog GCF/TCF9 and other putative transcriptionfactors SWISS-PROT: Q9Y224 Hypothetical protein CGI-99 Similarity toputative transcription factors ENSP00000216038 Hypothetical 55.2 kDaprotein Uncharacterized protein family UPFOO27 ENSP00000289509Hypothetical 80.5 kDa protein Similar to unknowns ENSP00000245838Hypothetical protein L0C57187 Similar to unknowns ENSP00000289996Hypothetical protein Similar to unknowns ENSP00000252137 DiGeorgesyndrome critical region Similar to unknowns gene DGSI proteinENSP00000256579 Hypothetical protein FLJ10330 Similar to unknownsENSP00000245651 C20orf158 protein Similar to unknowns SWISS-PROT: Q9BWJ5Hypothetical protein MGC3133 Similar to unknowns ENSP00000272091Hypothetical protein XP_089191 Similar to unknowns ENSP00000297526KIAA144O protein Similar to unknowns ENSP00000271942 Hypotheticalprotein FLJ21919 Similar to unknowns TREMBL: Q9BTU2 Hypothetical 31.5kDa protein Similar to unknowns TREMBL: Q8WVN3 Hypothetical proteinSimilar to unknowns a SWISS-PROT or ENSEMBL accession numbers are givenat http://srs.embl- heidelberg.de:8000 and http://www.ensembl.org. bDomains: RRM: RNA recognition motive; Bipartite NLS: Bipartite NuclearLocalization Signal; SPRY: SP1a/RY anodine receptor SPRY domain;G-patch: named after seven highly conserved glycines; KH: hnRNP Khomology domain; PWI: proline- tryptophan-isoleucine motifs; SAP:SAF-A/B, Acinus and PIAS motif; RS: Arginine-Serine repeats; Surp:Suppressor-of-white- apricot splicing regulator domain.

TABLE 3 Proteins Involved in Transcription, Translation, and OtherFunctions Acc. no. a Name Comments SWISS-PROT: P16991 CCAAT-bindingtranscription factor I subunit A ENSP00000271939 Interleukin enhancerbinding factor 2, 45 kD TREMBL: O15043 Death associated transcriptionfactor 1 ENSP00000266071 Death associated transcription factor-1 isoformb SWISS-PROT: P16383 GC-rich sequence DNA binding factor SWISS-PROT:P78347 general transcription factor II ENSP00000228251 Cold shock domainprotein A NP_005325 host cell factor CI SWISS-PROT: P49848 Transcriptioninitiation factor TFIID 70 kD subunit SWISS-PROT: P12956 ATP-dependentDNA helicase II, 70 kD subunit ENSP00000283131 SWI/SNF related, matrixassociated, actin dependent regulator of chromatin subfamily a, member 6SWISS-PROT: P30876 DNA-directed RNA polymerase II 140 kD SWISS-PROT:P24928 DNA-directed RNA polymerase II largest subunit SWISS-PROT: P02261Histone H2A- SWISS-PROT: P20670 H2A histone family member O SWISS-PROT:Q93080 H2B histone family several members possible SWISS-PROT: P09429High-mobility group protein 1 SWISS-PROT: O15347 High mobility group box4 ENSP00000275182 Histone deacetylase 2 SWISS-PROT: Q16576 Histoneacetyltransferase type B subunit 2 SWISS-PROT: P23396 40S ribosomalprotein S3 NP_000997 40S ribosomal protein S3A SWISS-PROT: P12750 40Sribosomal protein S4 SWISS-PROT: P22090 40S ribosomal protein S4Yisoform SWISS-PROT: P46782 40S ribosomal protein S5 SWISS-PROT: P2382140S ribosomal protein S7 SWISS-PROT: P09058 40S ribosomal protein S8SWISS-PROT: P46781 40S ribosomal protein S9 SWISS-PROT: P46783 40Sribosomal protein S10 ENSP00000237131 40S ribosomal protein S12SWISS-PROT: Q02546 40S ribosomal protein S13 SWISS-PROT: P11174 40Sribosomal protein S15 SWISS-PROT: P39027 40S ribosomal protein S15aSWISS-PROT: P17008 40S ribosomal protein S16 SWISS-PROT: P08708 40Sribosomal protein S17 SWISS-PROT: P25232 40S ribosomal protein S18SWISS-PROT: P39019 40S ribosomal protein S19 SWISS-PROT: P25111 40Sribosomal protein S25 SWISS-PROT: P30054 40S ribosomal protein S29SWISS-PROT: Q05472 40S ribosomal protein S30 SWISS-PROT: P04643 40Sribosomal protein S11 SWISS-PROT: P46777 60S ribosomal protein L5SWISS-PROT: P35268 60S ribosomal protein L22 SWISS-PROT: P29316 60Sribosomal protein L23a SWISS-PROT: P12947 60S ribosomal protein L31TREMBL Q8WT0 Signal recognition particle 9 kD SWISS-PROT: P09132 Signalrecognition particle 19 kD SWISS-PROT: Q9UHB9 Signal recognitionparticle 68 kD TREMBL: Q8WUK2 Signal recognition particle 68 kD isoformSWISS-PROT: Q76094 Signal recognition particle 72 kD SWISS-PROT: P04720Elongation factor 1 SWISS-PROT: P12270 Nucleoprotein TPR SWISS-PROT:P46940 Ras GTPase-activating- like ENSP00000268182 protein IQGAP1 (P195)SWISS-PROT: P52292 Importin alpha-2 subunit SWISS-PROT: O75909 Cyclin KSWISS-PROT: P78396 Cyclin A1 SWISS-PROT: P09874 poly(ADP-ribosyl)transferase SWISS-PROT: O43823 A-kinase anchor protein 8ENSP00000262971 PIAS1 ENSP00000296215 Smad nuclear-interacting protein 1ENSP00000234443 Protein kinase, interferon-inducible double stranded RNAdependent activator; protein activator of the interferon-induced proteinkinase ENSP00000300630 Ubiquitin ENSP00000271238 Phosphatase 2Ainhibitor SWISS-PROT: P19338 Nucleolin SWISS-PROT: P55081Microfibrillar-associated protein 1 SWISS-PROT: P11142 Heat shockcognate 71 kD protein ENSP00000286912 Dynein heavy chain SWISS-PROT:P08670 Vimentin ENSP00000243115 Tubulin, alpha ENSP00000259925 Tubulin,beta 5 a SWISSPROT or ENSEMBL accession numbers are given.(http://srs.embl- heidelberg.de:8000/srs5/ and www.ensembl.org)

TABLE 3 Transcription Factors TFFACTOR sorted by molecular weight (SZfield) Database: TFFACTOR TRANSFAC database, binding factor informationRelease 3.3, Jan 98 E. Wingender, R. Knueppel, P. Dietze, H. Karas(GBF-Braunschweig) 2,285 entries 1. T01627 8.3 kDa; lin-32 2. T02213 9.0kDa; PC4 p9 3. T01972 10.0 kDa; DMLP1 4. T01852 10.5 kDa; HMG I(Y) 5.T01980 10.5 kDa; HMG Y 6. T01714 11.5 kDa; HOXA10 PL2 7. T01851 11.5kDa; HMG I 8. T01859 11.8 kDa; HMGI-C 9. T01860 11.8 kDa; HMGI-C 10.T01322 12.1 kDa; ICER-Igamma 11. T01324 12.1 kDa; ICER-IIgamma 12.T01566 12.1 kDa; deltaMax 13. T02230 12.1 kDa; TFIIA-S 14. T02226 12.2kDa; TFIIA-S 15. T01630 12.3 kDa; Tal-2 16. T01631 12.3 kDa; Tal-2 17.T02180 12.5 kDa; SIII-p15 18. T02224 12.5 kDa; TFIIA-gamma 19. T0223212.5 kDa; TFIIA-S 20. T02269 12.5 kDa; SIII-p15 21. T01263 12.9 kDa;HAP3 22. T01809 13.0 kDa; Id3 23. T00367 13.1 kDa; Id3 24. T01811 13.1kDa; Id3 25. T02179 13.1 kDa; SIII-p18 26. T02268 13.1 kDa; SIII-p18 27.T01325 13.3 kDa; ATF-3deltaZIP 28. T01319 13.4 kDa; ICER 29. T01321 13.4kDa; ICER-I 30. T01323 13.4 kDa; ICER-II 31. T02228 13.5 kDa; TFIIA(13.5 kDa subunit) 32. T02150 13.9 kDa; SRB6 33. T02117 14.3 kDa;TAF(II)18 34. T02137 14.4 kDa; PC4 35. T02138 14.4 kDa; PC4 36. T0165414.6 kDa; HEN1 37. T00488 14.8 kDa; MATa1 38. T01655 14.8 kDa; HEN1 39.T01212 14.9 kDa; Id2 40. T00404 15.0 kDa; Id2 41. T01656 15.0 kDa; HEN242. T01657 15.0 kDa; HEN2 43. T01808 15.0 kDa; Id2 44. T00441 15.4 kDa;KBP-1 45. T00403 15.6 kDa; Id1 46. T01420 15.6 kDa; LIP 47. T01807 15.6kDa; Id1 48. T02274 15.6 kDa; Id1H′ 49. T00350 16.0 kDa; HAP3 50. T0181016.1 kDa; Id3/Heir-1 51. T02151 16.1 kDa; SRB7 52. T01801 16.2 kDa; Id153. T01384 16.5 kDa; pX 54. T01448 16.5 kDa; Tal-1beta 55. T01436 16.6kDa; MafF 56. T01658 16.6 kDa; Id4 57. T01600 16.8 kDa; CREMdeltaC-G 58.T01120 17.0 kDa; MCBF 59. T01650 17.0 kDa; HES-2 60. T01060 17.1 kDa;MNB1b 61. T00489 17.2 kDa; Max1 62. T01591 17.3 kDa; P (short form) 63.T01593 17.3 kDa; C1 (short form) 64. T01301 17.4 kDa; E4 65. T01606 17.4kDa; Id1.25 66. T01639 17.4 kDa; INO4 67. T02311 17.4 kDa; CSE2 68.T01434 17.5 kDa; MafK 69. T01435 17.5 kDa; MafK 70. T01622 17.6 kDa;ASH-3a 71. T01745 17.6 kDa; HOXC6 (PRI) 72. T01743 17.8 kDa; HOXC6 (PRI)73. T02249 17.8 kDa; Lmo1 74. T01742 17.9 kDa; HOXC6 75. T02116 17.9kDa; TAF(II)20 76. T01274 18.0 kDa; DBF-A 77. T02254 18.0 kDa;PEBP2beta3 78. T01437 18.1 kDa; MafG 79. T00523 18.3 kDa; Myn 80. T0156718.3 kDa; Max2 81. T02251 18.3 kDa; Lmo2 82. T02250 18.4 kDa; Lmo2 83.T01652 18.5 kDa; HES-5 84. T02089 18.7 kDa; mat-Pc 85. T01636 18.8 kDa;X-Twist 86. T00127 19.0 kDa; CHOP-10 87. T00224 19.0 kDa; EF1 88. T0029919.0 kDa; GADD 153 89. T01206 19.0 kDa; EF1 90. T02139 19.0 kDa; PC4 91.T01651 19.1 kDa; HES-3 92. T00197 19.3 kDa; Dr1 93. T01687 19.3 kDa;Pcr1 94. T00043 19.5 kDa; ARG RI 95. T01644 19.9 kDa; E(spl)m5 96.T01447 20.0 kDa; HEN1 97. T02216 20.0 kDa; TFIIA-alpha/beta precursor(major) 98. T02217 20.0 kDa; TFIIA-alpha/beta precursor (minor) 99.T01646 20.3 kDa; E(spl)m8 100. T00486 20.4 kDa; MATalpha1 101. T0131020.4 kDa; S-CREM 102. T01313 20.6 kDa; ATF-3 103. T01095 20.7 kDa; LRF-1104. T01612 20.7 kDa; Meso1 105. T01645 20.7 kDa; E(spl)m7 106. T0197120.8 kDa; MLP 107. T01623 20.9 kDa; ASH-3b 108. T01637 20.9 kDa; EC2109. T02221 20.9 kDa; Bro 110. T01275 21.0 kDa; mat-Mc 111. T01635 21.2kDa; M-Twist 112. T01065 21.5 kDa; PEBP2beta2 113. T02259 21.5 kDa;PEBP2beta 114. T02126 21.6 kDa; TAF(II)30alpha 115. T02309 21.6 kDa;MET28 116. T01754 21.7 kDa; HOXD8 117. T02118 21.7 kDa; TAF(II)30 118.T01890 21.8 kDa; Brn-5(c7) 119. T02222 21.8 kDa; Bgb 120. T00274 22.0kDa; Emc 121. T02255 22.0 kDa; PEBP2beta1 122. T02131 22.1 kDa;TAF(II)30beta 123. T00799 22.4 kDa; TBP-1 124. T00800 22.4 kDa; TBP-2125. T01621 22.4 kDa; ASH-1 126. T00005 22.7 kDa; Ac 127. T01813 22.7kDa; Pax-3B 128. T00616 22.8 kDa; NF-YB 129. T02147 22.9 kDa; SRB2 130.T01601 23.0 kDa; CREMdeltaC-F 131. T02275 23.1 kDa; SUP 132. T00216 23.3kDa; C/EBPgamma 133. T02114 23.3 kDa; TAF(II)28 134. T01018 23.6 kDa;CAP 135. T01569 23.8 kDa; Th1 136. T00997 23.9 kDa; SRY 137. T01735 23.9kDa; HOXB7 138. T00179 24.0 kDa; CUP2 139. T01704 24.0 kDa; HOXA7 140.T01734 24.0 kDa; HOXB7 141. T01812 24.1 kDa; Pax-3A 142. T01316 24.2kDa; CREMgamma 143. T00487 24.3 kDa; MATalpha2 144. T01803 24.3 kDa;CREMalpha 145. T00516 24.4 kDa; mtTF1 146. T02061 24.4 kDa; K-2b 147.T01987 24.5 kDa; SRY 148. T01887 24.6 kDa; Brn-4 149. T02211 24.6 kDa;BTEB2 150. T01779 24.7 kDa; GLO 151. T02025 24.7 kDa; C/EBPalpha(p30)152. T01059 24.8 kDa; MNB1a 153. T01619 24.8 kDa; MASH-1 154. T0008725.0 kDa; CBF-A 155. T00484 25.0 kDa; MASH-1 156. T00520 25.0 kDa; Myf-4157. T01741 25.0 kDa; HOXC5 158. T01736 25.1 kDa; HOXB7 159. T00528 25.2kDa; myogenin 160. T01565 25.3 kDa; Mad 161. T01733 25.3 kDa; HOXB6 162.T00795 25.4 kDa; TBP 163. T01315 25.4 kDa; CREMbeta 164. T01778 25.4kDa; GLO 165. T02198 25.4 kDa; FosB/SF 166. T00849 25.5 kDa; TRF 167.T01314 25.5 kDa; CREMalpha 168. T01732 25.5 kDa; HOXB6 169. T02027 25.5kDa; C/EBPalpha(p30) 170. T02026 25.6 kDa; C/EBPalpha(p30) 171. T0127825.7 kDa; HOXA7 172. T01533 25.7 kDa; myogenin 173. T01620 25.7 kDa;MASH-1 174. T01531 25.8 kDa; myogenin 175. T00180 25.9 kDa; CYS3 176.T01082 25.9 kDa; NRL 177. T01438 26.1 kDa; NRL 178. T01564 26.1 kDa;Mxi1 179. T01740 26.2 kDa; HOXB9 180. T01008 26.3 kDa; DEF A 181. T0153826.4 kDa; MRF4 182. T01588 26.4 kDa; GL1 183. T00967 26.5 kDa; E1A 12Sprotein 184. T01729 26.5 kDa; HOXB4 185. T00888 26.6 kDa; v-Fos 186.T02039 26.6 kDa; HAC1 187. T01746 26.7 kDa; HOXC6 (PRII) 188. T0175326.7 kDa; HOXD4 189. T00633 26.8 kDa; N-Oct-Sb 190. T00798 26.9 kDa; TBP191. T00923 26.9 kDa; Zta 192. T01057 26.9 kDa; lin-31 193. T01744 26.9kDa; HOXC6 (PRII) 194. T01747 26.9 kDa; HOXC6 (PRII) 195. T00512 27.0kDa; MRF4 196. T00522 27.0 kDa; Myf-6 197. T01537 27.0 kDa; MRF4 198.T01777 27.0 kDa; GP 199. T01255 27.1 kDa; DAT1 200. T01539 27.1 kDa;MRF4 201. T00171 27.2 kDa; C/EBPepsilon 202. T02045 27.2 kDa; Flh 203.T02210 27.2 kDa; BTEB 204. T02212 27.2 kDa; BTEB 205. T01752 27.3 kDa;HOXD4 206. T01776 27.3 kDa; APETALA3 207. T02046 27.3 kDa; Gsc 208.T02060 27.3 kDa; K-2a 209. T01484 27.4 kDa; Cdx-1 210. T02044 27.4 kDa;Flh 211. T02049 27.4 kDa; Gsc B 212. T02132 27.4 kDa; TAF(II)30 213.T02141 27.4 kDa; OCA-B 214. T02256 27.4 kDa; AML1a 215. T01515 27.5 kDa;Pur factor 216. T01728 27.5 kDa; HOXB4 217. T02069 27.5 kDa; Msx-1 218.T01727 27.6 kDa; HOXB4 219. T01737 27.6 kDa; HOXB8 220. T02142 27.6 kDa;OCA-B 221. T00485 27.7 kDa; MASH-2 222. T01749 27.7 kDa; HOXC8 223.T01726 27.8 kDa; HOXB4 224. T00376 27.9 kDa; HOXD4 225. T00347 28.0 kDa;HAP2 226. T01370 28.0 kDa; p28 modulator 227. T02047 28.0 kDa; Gsc 228.T01534 28.2 kDa; Myf-5 229. T01535 28.2 kDa; Myf-5 230. T02074 28.2 kDa;Msx-2 231. T02077 28.2 kDa; Msx-2 232. T01090 28.3 kDa; TAF-1 233.T01846 28.3 kDa; TCF-1D 234. T02170 28.3 kDa; TFIIF-beta 235. T0052128.4 kDa; Myf-5 236. T00583 28.4 kDa; C/EBPdelta 237. T01536 28.4 kDa;Myf-5 238. T01706 28.4 kDa; HOXA7 239. T01986 28.4 kDa; SRY 240. T0199928.4 kDa; Cdx-1 241. T02007 28.4 kDa; Dlx-1 242. T02169 28.4 kDa;TFIIF-beta 243. T02195 28.4 kDa; TBP 244. T00109 28.6 kDa; C/EBPdelta245. T00949 28.6 kDa; Myf-5 246. T01114 28.6 kDa; C/EBPdelta 247. T0198128.6 kDa; TCF-1F 248. T00632 28.7 kDa; N-Oct-5a 249. T00902 28.7 kDa;XBP-1 250. T00926 28.7 kDa; SUM-1 251. T01632 28.7 kDa; Lyl-1 252.T01401 28.8 kDa; Spi-B 253. T01592 28.8 kDa; C1 (long form) 254. T0177328.8 kDa; AG 255. T02075 28.8 kDa; Msx-2 256. T01880 28.9 kDa; Brn-3b257. T02076 28.9 kDa; Msx-2 258. T00003 29.0 kDa; AS-C T3 259. T0108629.0 kDa; beta-1 260. T01982 29.0 kDa; TCF-1G 261. T02113 29.0 kDa;TAF(II)31 262. T00871 29.1 kDa; USF 263. T01116 29.1 kDa; SAP1 264.T02099 29.1 kDa; Zen-2 265. T00008 29.2 kDa; Adf-1 266. T00160 29.2 kDa;CPC1 267. T00377 29.2 kDa; HOXA5 268. T00968 29.2 kDa; ATF-1 269. T0107229.2 kDa; TEF 270. T01304 29.2 kDa; ATF-1 271. T02105 29.2 kDa;C/EBPbeta(p34) 272. T02125 29.3 kDa; TAF(II)40 273. T00925 29.4 kDa;AMT1 274. T01462 29.4 kDa; Fra-1 275. T01702 29.4 kDa; HOXA5 276. T0173029.4 kDa; HOXB5 277. T02050 29.4 kDa; Gtx 278. T02090 29.4 kDa; Phox-2279. T01731 29.5 kDa; HOXB5 280. T01648 29.6 kDa; HES-1 281. T01649 29.7kDa; HES-1 282. T00349 29.8 kDa; HAP2 283. T00292 29.9 kDa; Fra-1 284.T01249 29.9 kDa; BUF1 285. T00597 30.0 kDa; NF-kappaE2 286. T01221 30.0kDa; NF-kappaE2 287. T01277 30.0 kDa; spE2F 288. T01762 30.0 kDa; HOXD12289. T01775 30.0 kDa; APETALA1 290. T02092 30.0 kDa; Prh 291. T0222530.0 kDa; TFIIA-L 292. T01208 30.1 kDa; Fra-1 293. T01290 30.1 kDa;MATalpha1 294. T01872 30.1 kDa; Oct-4B 295. T02172 30.1 kDa; TFIIF-beta296. T01000 30.2 kDa; TCF-1B 297. T01633 30.2 kDa; Lyl-1 298. T0209130.2 kDa; Prh 299. T00999 30.3 kDa; TCF-1A 300. T01001 30.3 kDa; TCF-1C301. T01763 30.3 kDa; HOXD12 302. T01317 30.4 kDa; CREMepsilon 303.T02068 30.4 kDa; PU.1 304. T02108 30.4 kDa; CREMtau1 305. T02018 30.5kDa; En-2 306. T02070 30.5 kDa; Msx-1 307. T00702 30.7 kDa; PU.1 308.T02058 30.8 kDa; IPF1 309. T02072 30.8 kDa; Msx-1 310. T00845 30.9 kDa;Tra-1 (short form) 311. T01474 30.9 kDa; Athb-1 312. T01996 31.0 kDa;dJRA 313. T02057 31.0 kDa; IPF1 314. T02071 31.0 kDa; Msx-1 315. T0207331.0 kDa; Msx-1 316. T00321 31.3 kDa; GCN4 317. T00267 31.4 kDa; GATA-1318. T01426 31.4 kDa; HOXD8 319. T00017 31.5 kDa; C/EBPbeta 320. T0045931.5 kDa; C/EBPbeta 321. T02082 31.6 kDa; Otx2 322. T02083 31.6 kDa;Otx2 323. T02109 31.6 kDa; CREMtau2 324. T00653 31.7 kDa; Oct-5 325.T01720 31.7 kDa; HOXB1 326. T00209 31.8 kDa; E1A 13S protein 327. T0176131.8 kDa; HOXD11 328. T01389 31.9 kDa; LEF-1S 329. T01475 31.9 kDa;Athb-2 330. T01759 31.9 kDa; HOXD11 331. T00961 32.0 kDa; ANF-2 332.T01381 32.0 kDa; deltaCREB 333. T01719 32.1 kDa; HOXB1 334. T01816 32.1kDa; Mab-18 (284 AA) 335. T02174 32.1 kDa; TFIIF-beta 336. T00815 32.2kDa; TFIIA 337. T02227 32.2 kDa; TFIIA (32 kDa subunit) 338. T00524 32.3kDa; MyoD 339. T01093 32.4 kDa; CPRF-3 340. T01764 32.4 kDa; HOXD13 341.T00893 32.5 kDa; v-Jun 342. T01532 32.5 kDa; myogenin 343. T01893 32.6kDa; TCFbeta1 344. T02166 32.6 kDa; TFIIE-beta 345. T01605 32.7 kDa;SGC1 346. T01891 32.7 kDa; Brn-5 347. T02111 32.7 kDa; TBP 348. T0050032.8 kDa; MCM1 349. T00325 32.9 kDa; Pit-1 350. T01172 32.9 kDa; Pit-1351. T01516 32.9 kDa; Pit-1b 352. T01888 32.9 kDa; Brn-5(c2) 353. T0112833.0 kDa; MyoD 354. T01551 33.0 kDa; MyoD 355. T02163 33.0 kDa;TFIIE-beta 356. T02238 33.0 kDa; TFIIE-beta 357. T01889 33.1 kDa;Brn-5(c1) 358. T01071 33.2 kDa; Hlf 359. T01641 33.2 kDa; PHO80 360.T01817 33.2 kDa; Mab-18 (296 AA) 361. T02031 33.2 kDa; HSF24 362. T0219633.2 kDa; JunD 363. T01716 33.3 kDa; HOXA11 364. T01751 33.3 kDa; HOXD1365. T01876 33.3 kDa; Brn-3a 366. T02304 33.4 kDa; Pur-1 367. T0012833.5 kDa; HOXA4 368. T00874 33.5 kDa; USF 369. T01760 33.5 kDa; HOXD11370. T02002 33.5 kDa; Cdx-2 371. T01691 33.6 kDa; TTP 372. T01847 33.6kDa; TCF-1 373. T01878 33.6 kDa; Brn-3a(s) 374. T02003 33.6 kDa; Cdx-3375. T01063 33.7 kDa; PEBP2alphaA2 376. T01718 33.8 kDa; HOXB1 377.T01800 33.8 kDa; Tal-1 378. T02020 33.8 kDa; En-2 379. T00134 33.9 kDa;c-Jun 380. T01078 33.9 kDa; GBF1 381. T02188 33.9 kDa; TFIIH-p34 382.T00615 34.0 kDa; NF-YA 383. T01513 34.0 kDa; AEF-1 384. T01836 34.0 kDa;Sox-2 385. T00690 34.1 kDa; PHO4 386. T01628 34.1 kDa; Ato 387. T0175034.1 kDa; HOXD1 388. T01837 34.1 kDa; Sox-2 389. T00526 34.2 kDa; MyoD390. T01241 34.2 kDa; INO2 391. T01388 34.2 kDa; C/EBP 392. T01675 34.2kDa; Nkx-2.5 393. T02019 34.2 kDa; En-2 394. T02234 34.2 kDa; TFIIB 395.T00790 34.3 kDa; Tal-1 396. T00881 34.3 kDa; VBP 397. T01453 34.3 kDa;v-Fos 398. T01799 34.3 kDa; Tal-1 399. T01976 34.3 kDa; c-Jun 400.T02149 34.3 kDa; SRB5 401. T02233 34.3 kDa; TFIIB 402. T00183 34.4 kDa;DBP 403. T01242 34.4 kDa; SNP1 404. T02054 34.4 kDa; Hox11 405. T0215834.4 kDa; TFIIB 406. T00519 34.5 kDa; Myf-3 407. T00525 34.5 kDa; MyoD408. T00548 34.5 kDa; NF-AB 409. T00707 34.5 kDa; PUF-I 410. T01703 34.5kDa; HOXA4 411. T02014 34.5 kDa; En-1 412. T00293 34.6 kDa; FRG Y1 413.T02055 34.6 kDa; Hox11 414. T00796 34.7 kDa; TBP 415. T02009 34.7 kDa;Dlx-2 416. T02160 34.7 kDa; TFIIB 417. T00818 34.8 kDa; TFIIB 418.T02159 34.8 kDa; TFIIB 419. T00348 34.9 kDa; HAP2 420. T00437 34.9 kDa;JunD 421. T01826 34.9 kDa; Pax-8c 422. T02197 34.9 kDa; JunD 423. T0016535.0 kDa; deltaCREB 424. T00166 35.0 kDa; deltaCREB 425. T00816 35.0kDa; TFIIA 426. T00846 35.0 kDa; TREB-1 427. T01755 35.0 kDa; HOXD9 428.T01938 35.0 kDa; IkappaB-alpha 429. T02022 35.0 kDa; C/EBPbeta 430.T01311 35.1 kDa; deltaCREB 431. T01552 35.2 kDa; TFEC 432. T01701 35.2kDa; HOXA4 433. T01939 35.2 kDa; IkappaB-alpha 434. T01990 35.2 kDa;Fra-2 435. T01991 35.2 kDa; Fra-2 436. T02005 35.2 kDa; Dll 437. T0219435.2 kDa; TFIIH-KIN28 438. T01881 35.3 kDa; Brn-3b 439. T02199 35.3 kDa;Fra-2 440. T00186 35.4 kDa; DbpB 441. T00910 35.4 kDa; YB-1 442. T0193735.4 kDa; IkappaB-alpha 443. T01978 35.4 kDa; JunD 444. T02200 35.4 kDa;Fra-2 445. T00421 35.5 kDa; IREBF-1 446. T01433 35.5 kDa; MafB 447.T02202 35.5 kDa; MafB 448. T00950 35.6 kDa; IkappaB-alpha 449. T0142435.6 kDa; HOXD9 450. T01681 35.6 kDa; PTFdelta 451. T00107 35.7 kDa;C/EBPalpha 452. T00133 35.7 kDa; c-Jun 453. T00235 35.7 kDa; EFIA 454.T01570 35.7 kDa; FlbD 455. T00236 35.8 kDa; EFIA 456. T00436 35.8 kDa;JunB 457. T00691 35.8 kDa; Pit-1a 458. T01439 35.8 kDa; kreisler 459.T02187 35.8 kDa; TFIIH-MAT1 460. T00131 35.9 kDa; c-Jun 461. T01977 35.9kDa; JunB 462. T00132 36.0 kDa; c-Jun 463. T00291 36.0 kDa; FosB 464.T00538 36.0 kDa; NF-1 465. T01696 36.0 kDa; HOXA1 466. T00581 36.1 kDa;C/EBPbeta 467. T01055 36.2 kDa; Slp1 468. T01098 36.2 kDa; EmBP-1 469.T01540 36.2 kDa; Nau 470. T01992 36.2 kDa; abd-A 471. T00110 36.5 kDa;CeMyoD 472. T00423 36.5 kDa; IRF-1 473. T01309 36.6 kDa; CREMtau 474.T01589 36.6 kDa; MybSt1 475. T01695 36.6 kDa; HOXA1 476. T01919 36.6kDa; CREMtau 477. T02112 36.6 kDa; TBP 478. T00163 36.7 kDa; CREB 479.T00937 36.7 kDa; HBP-1a 480. T00989 36.7 kDa; CREB 481. T01602 36.7 kDa;CREMtaualpha 482. T00938 36.8 kDa; HBP-1b 483. T01970 36.8 kDa; Mec-3484. T00157 36.9 kDa; CP1B 485. T01386 36.9 kDa; C/EBP 486. T01392 36.9kDa; GABP-beta2 487. T01404 36.9 kDa; GABP-beta2 488. T00164 37.0 kDa;CREB 489. T00185 37.0 kDa; DbpA 490. T00345 37.0 kDa; H 491. T00547 37.0kDa; NF-AB 492. T01555 37.0 kDa; USF2 493. T01892 37.0 kDa; Sprm-1 494.T00424 37.1 kDa; IRF-1 495. T00498 37.1 kDa; MBP-1 (2) 496. T01076 37.1kDa; Mec-3 497. T02240 37.1 kDa; TFIIE-beta 498. T00294 37.2 kDa; FRG Y2499. T01595 37.2 kDa; CBF-C 500. T00422 37.3 kDa; IRF-1 501. T02079 37.3kDa; Otx1 502. T01785 37.4 kDa; xMEF-2 503. T02080 37.5 kDa; Otx1 504.T00105 37.6 kDa; C/EBPalpha 505. T01607 37.6 kDa; E2F-5 506. T02081 37.6kDa; Otx1 507. T02184 37.6 kDa; TFIIH-cyclin H 508. T00104 37.7 kDa;C/EBPalpha 509. T00108 37.7 kDa; C/EBPalpha 510. T00794 37.7 kDa; TBP511. T01050 37.7 kDa; HNF-3gamma 512. T01677 37.7 kDa; LKLF 513. T0220137.7 kDa; c-Maf (short form) 514. T02220 37.7 kDa; AML1DeltaN 515.T01676 37.8 kDa; EKLF 516. T02093 37.8 kDa; Ro 517. T02155 37.8 kDa;SRB11 518. T00677 37.9 kDa; Pax-1 519. T01668 37.9 kDa; MATH-1 520.T00651 38.0 kDa; Oct-4 521. T00858 38.0 kDa; TTF-1 522. T00859 38.0 kDa;TTF-1 523. T00971 38.0 kDa; IkappaB-beta 524. T01604 38.0 kDa; dCREB2-a525. T00004 38.1 kDa; Sc 526. T01407 38.1 kDa; NRF-2gamma1 527. T0175738.4 kDa; HOXD10 528. T02087 38.4 kDa; Pbx-1b 529. T02088 38.4 kDa;Pbx-1b 530. T00797 38.5 kDa; TBP 531. T01303 38.5 kDa; CREB-2 532.T01425 38.5 kDa; HOXD10 533. T02098 38.5 kDa; TTF-1 534. T00652 38.6kDa; Oct-4A 535. T00746 38.6 kDa; SGF-3 536. T00856 38.6 kDa; TTF-1 537.T00857 38.6 kDa; TTF-1 538. T01012 38.6 kDa; xMEF-2 539. T01629 38.6kDa; MATH-2 540. T01432 38.7 kDa; c-Maf 541. T01957 38.7 kDa; Isl-1 542.T00744 38.8 kDa; SGF-1 543. T01079 38.8 kDa; GBF2 544. T01430 38.9 kDa;v-Maf 545. T01431 38.9 kDa; c-Maf (long form) 546. T00125 39.0 kDa;c-Fos 547. T00268 39.0 kDa; GABP 548. T00304 39.0 kDa; GATA-1A 549.T01017 39.0 kDa; CRE-BP2 550. T01035 39.0 kDa; Isl-1 551. T01956 39.0kDa; Isl-1 552. T02186 39.0 kDa; TFIIH-MO15 553. T00819 39.1 kDa; TFIIB554. T02161 39.1 kDa; TFIIB 555. T01653 39.2 kDa; Delilah 556. T0091739.3 kDa; Zen-1 557. T01491 39.3 kDa; IRF-2 558. T02301 39.3 kDa; CTF-7559. T02319 39.3 kDa; PEBP2alphaA/til-1(U) 560. T00080 39.4 kDa; CBF1561. T01884 39.4 kDa; Brn-4 562. T01885 39.4 kDa; Brn-4 563. T01886 39.4kDa; Brn-4 564. T00425 39.5 kDa; IRF-2 565. T00732 39.5 kDa; Ro 566.T01625 39.7 kDa; NeuroD 567. T02295 39.7 kDa; TFIIIA 568. T02062 39.8kDa; KN1 569. T02312 39.8 kDa; GATA-1B 570. T01898 39.9 kDa; I-POU 571.T00154 40.0 kDa; CP1A 572. T00200 40.0 kDa; DTF 573. T00272 40.0 kDa;Eve 574. T00399 40.0 kDa; IBF 575. T00416 40.0 kDa; IkappaB-beta 576.T00466 40.0 kDa; LF-A1 577. T00700 40.0 kDa; PTF 578. T00708 40.0 kDa;p40x 579. T00863 40.0 kDa; Ubx 580. T00868 40.0 kDa; URSF 581. T0110640.0 kDa; EBP40 582. T01626 40.0 kDa; NeuroD 583. T01674 40.0 kDa; BETA3584. T02015 40.0 kDa; En-1 585. T01899 40.2 kDa; tI-POU 586. T02032 40.2kDa; HSF30 587. T02276 40.2 kDa; ATBP 588. T00782 40.3 kDa; TAF(II)55589. T01259 40.3 kDa; ARG RIII 590. T02063 40.3 kDa; Knox3 591. T0128840.6 kDa; PHD1 592. T01979 40.6 kDa; TCF-1E 593. T00123 40.7 kDa; c-Fos594. T01395 40.7 kDa; HBP-1a(c14) 595. T00122 40.8 kDa; c-Fos 596.T01400 40.8 kDa; Ets-1 deltaVII 597. T01698 40.8 kDa; HOXA2 598. T0169940.8 kDa; HOXA2 599. T02205 40.8 kDa; c-Fos 600. T00124 40.9 kDa; c-Fos601. T00083 41.0 kDa; CBF (2) 602. T00088 41.0 kDa; CBF-B 603. T0082941.0 kDa; TGA1a 604. T00924 41.0 kDa; CIIIB1 605. T01700 41.0 kDa; HOXA2606. T02016 41.0 kDa; En-1 607. T01080 41.1 kDa; GBF3 608. T00769 41.2kDa; Sry-beta 609. T01391 41.3 kDa; GABP-beta1 610. T01403 41.3 kDa;GABP-beta1 611. T02241 41.3 kDa; PEBP2alphaB2 612. T00265 41.4 kDa;Erg-1 613. T01643 41.4 kDa; H 614. T01715 41.4 kDa; HOXA10 615. T0229441.4 kDa; XFD-2 616. T01440 41.6 kDa; NF-E2 p45 617. T01441 41.6 kDa;NF-E2 p45 618. T01452 41.6 kDa; v-Fos 619. T01843 41.6 kDa; Sox-18 620.T02231 41.6 kDa; TFIIA-L 621. T01482 41.7 kDa; Exd 622. T01825 41.7 kDa;Pax-8b 623. T01286 41.8 kDa; Rox1 624. T02052 41.8 kDa; CREB-2 625.T02229 41.8 kDa; TFIIA-L 626. T01373 42.0 kDa; CBTF 627. T01822 42.0kDa; Pax-2b 628. T01968 42.0 kDa; LH-2 629. T02024 42.0 kDa; Evx-1 630.T00070 42.1 kDa; Pax-5 631. T01692 42.1 kDa; T3R-beta1 632. T01201 42.2kDa; Pax-5 633. T01382 42.3 kDa; CRE-BP2 634. T01823 42.3 kDa; Pax-2635. T02298 42.3 kDa; NF-1A3 636. T02021 42.4 kDa; Evx-1 637. T0140642.5 kDa; NRF-2beta1 638. T02103 42.5 kDa; p53as 639. T00243 42.6 kDa;EGR3 640. T00305 42.6 kDa; GATA-1 641. T01550 42.7 kDa; dDP 642. T0002642.8 kDa; Antp 643. T00306 42.8 kDa; GATA-1 644. T01877 42.8 kDa;Brn-3a(1) 645. T01958 42.8 kDa; Lmx-1 646. T02252 42.8 kDa; Ldb1 647.T02097 42.9 kDa; STM 648. T00135 43.0 kDa; c-Jun 649. T00242 43.0 kDa;EGR2 650. T00414 43.0 kDa; IkappaB-beta 651. T00446 43.0 kDa; 43Kprotein 652. T01096 43.0 kDa; GHF3 653. T01380 43.0 kDa; CREB 654.T01680 43.0 kDa; PTFgamma 655. T01827 43.0 kDa; Pax-8d 656. T01832 43.1kDa; v-Qin 657. T01842 43.1 kDa; WT1 I-del2 658. T01429 43.2 kDa; Sox-5659. T02023 43.2 kDa; Evx-1 660. T01722 43.5 kDa; HOXB3 661. T01806 43.5kDa; p53 662. T01896 43.5 kDa; t-Pou2 663. T01866 43.6 kDa; Oct-2.4 664.T00671 43.7 kDa; p53 665. T01456 43.7 kDa; ISGF-3gamma 666. T01590 43.8kDa; P (long form) 667. T01965 43.8 kDa; Lim-3 668. T02253 43.8 kDa;Ch-runtB2 669. T01874 43.9 kDa; Oct-11 670. T00877 44.0 kDa; USF 671.T00878 44.0 kDa; USF2 672. T01091 44.0 kDa; CPRF-1 673. T01546 44.0 kDa;E2F-4 674. T01942 44.0 kDa; IkappaB-gamma2 675. T01963 44.0 kDa; Lim-3676. T01964 44.0 kDa; Lim-3 677. T02115 44.0 kDa; USF2 678. T00930 44.1kDa; LEF-1 679. T00802 44.2 kDa; TCF-1alpha 680. T01723 44.3 kDa; HOXB3681. T01414 44.4 kDa; Net 682. T01724 44.4 kDa; HOXB3 683. T02185 44.4kDa; TFIIH-p44 684. T01051 44.5 kDa; XFD-1 685. T01413 44.5 kDa; Net686. T01830 44.5 kDa; XFD-1′ 687. T01960 44.5 kDa; Lim-1 688. T0027844.6 kDa; delta factor 689. T00162 44.7 kDa; CreA 690. T00865 44.7 kDa;UCRBP 691. T01841 44.7 kDa; WT1-del2 692. T02128 44.7 kDa; SAP-1b 693.T00678 44.8 kDa; Pax-2a 694. T00915 44.8 kDa; YY1 695. T00955 44.8 kDa;DSXF 696. T01541 44.8 kDa; Esc1 697. T01954 44.8 kDa; vHNF-1C 698.T01959 44.8 kDa; Lim-1 699. T01961 44.8 kDa; Lim-1 700. T00250 44.9 kDa;Elk-1 701. T01962 44.9 kDa; Lim-1 702. T00051 45.0 kDa; ATF 703. T0006945.0 kDa; BrlA 704. T00215 45.0 kDa; muEBP-C2 705. T00527 45.0 kDa; MyoD706. T00563 45.0 kDa; NF-muE3 707. T00834 45.0 kDa; TIN-1 708. T0099545.0 kDa; DBSF 709. T01052 45.0 kDa; XFD-1+ 710. T01107 45.0 kDa; EBP45711. T01215 45.0 kDa; NF-muE3 712. T01353 45.0 kDa; PPARbeta 713. T0136545.0 kDa; p45 714. T02096 45.0 kDa; Scr 715. T01548 45.1 kDa; DP-1 716.T01549 45.1 kDa; DP-1 717. T01834 45.1 kDa; Axial 718. T01838 45.2 kDa;Sox-4 719. T01850 45.2 kDa; DSP1 720. T02193 45.2 kDa; TFIIH-CCL1 721.T00656 45.3 kDa; Oct-6 722. T00178 45.4 kDa; CTF-3 723. T00969 45.5 kDa;Oct-6 724. T01820 45.5 kDa; Gsb 725. T02288 45.5 kDa; HFH-1 726. T0044545.6 kDa; Kni 727. T01867 45.7 kDa; Oct-2.6 728. T01075 45.8 kDa; lin-11729. T01239 45.8 kDa; CAD1 730. T01921 45.9 kDa; Gfi-1 731. T00141 46.0kDa; c-Myc 732. T00786 46.0 kDa; TAF-II 733. T00836 46.0 kDa; T3R 734.T00837 46.0 kDa; T3R 735. T00838 46.0 kDa; T3R 736. T00839 46.0 kDa; T3R737. T00840 46.0 kDa; T3R 738. T00854 46.0 kDa; T3R 739. T01385 46.0kDa; CREB 740. T00763 46.1 kDa; SRF 741. T00149 46.2 kDa; COUP 742.T01543 46.3 kDa; E2F-1 743. T01915 46.3 kDa; NF-1X1 744. T01409 46.4kDa; p38erg 745. T01265 46.5 kDa; MAC1 746. T01647 46.5 kDa; Dpn 747.T02279 46.5 kDa; ZNF174 748. T01122 46.6 kDa; Pax-6 749. T01481 46.6kDa; Pbx-1a 750. T02176 46.6 kDa; TFIIF-beta 751. T00681 46.7 kDa; Pax-6752. T01967 46.7 kDa; LH-2 753. T00737 46.8 kDa; SAP-1a 754. T00841 46.8kDa; T3R-alpha 755. T01152 46.8 kDa; T3R-alpha1 756. T01173 46.8 kDa;T3R-alpha 757. T01342 46.8 kDa; T3R-alpha1 758. T01351 46.8 kDa;T3R-alpha 759. T01554 46.8 kDa; Mi 760. T01683 46.8 kDa; PTFbeta 761.T01928 46.8 kDa; Bcl-3 762. T00295 46.9 kDa; Ftz 763. T00630 46.9 kDa;N-Oct-3 764. T01542 46.9 kDa; E2F-1 765. T01553 46.9 kDa; Mi 766. T0190346.9 kDa; NF-1X 767. T00029 47.0 kDa; AP-1 768. T00045 47.0 kDa; ARP-1769. T00388 47.0 kDa; H1TF2 770. T00442 47.0 kDa; 47-kDa CRE bind. prot.771. T00539 47.0 kDa; NF-1 772. T01690 47.1 kDa; Elt-2 773. T01873 47.1kDa; N-Oct-3 774. T00900 47.2 kDa; WT1 I-KTS 775. T01524 47.2 kDa;N-Oct-3 776. T01276 47.3 kDa; Sox-4 777. T02321 47.3 kDa; SRE-ZBP 778.T00552 47.4 kDa; NF-1B2 779. T01526 47.4 kDa; Brachyury 780. T01966 47.4kDa; LH-2 781. T01544 47.5 kDa; E2F-2 782. T01840 47.5 kDa; WT1 I 783.T02236 47.6 kDa; TFIIE 784. T02237 47.6 kDa; TFIIE-alpha 785. T0230047.6 kDa; CTF-5 786. T00882 47.8 kDa; VDR 787. T01774 47.8 kDa; APETALA2788. T00177 47.9 kDa; CTF-2 789. T00806 47.9 kDa; TEF-1 790. T01124 47.9kDa; TEF-1 791. T01768 47.9 kDa; MEF-2C/delta32 792. T00310 48.0 kDa;GATA-3 793. T00439 48.0 kDa; KBF1 794. T00568 48.0 kDa; NF-E1c 795.T01213 48.0 kDa; KBF1 796. T02156 48.0 kDa; Esc 797. T02157 48.0 kDa;TFIIA 798. T00035 48.1 kDa; AP-2 799. T01824 48.1 kDa; Pax-8a 800.T00402 48.2 kDa; ICSBP 801. T01468 48.2 kDa; ZID 802. T01469 48.2 kDa;Ik-1 803. T01814 48.2 kDa; Pax-6/Pd-5a 804. T01821 48.2 kDa; Gsbn 805.T00885 48.3 kDa; VDR 806. T01916 48.3 kDa; NF-1X2 807. T02036 48.3 kDa;CRE-BP3 808. T02038 48.3 kDa; ICSBP 809. T00682 48.4 kDa; Pax[zf-a] 810.T00716 48.5 kDa; RAR 811. T01049 48.5 kDa; HNF-3B 812. T00490 48.6 kDa;MAZ 813. T02235 48.6 kDa; PEBP2alphaB1 814. T02245 48.7 kDa; AML1b 815.T00140 48.8 kDa; c-Myc 816. T00371 48.8 kDa; HNF-3 817. T00610 48.8 kDa;NF-1X 818. T02303 48.8 kDa; Pur-1 819. T00142 48.9 kDa; c-Myc 820.T01828 48.9 kDa; Pax-8 821. T01833 48.9 kDa; c-Qin 822. T01839 48.9 kDa;WT1-KTS 823. T02056 48.9 kDa; CRE-BP1 824. T00106 49.0 kDa; C/EBP 825.T00143 49.0 kDa; c-Myc 826. T01599 49.0 kDa; LCR-F1 827. T02165 49.0kDa; TFIIE-alpha 828. T01545 49.1 kDa; E2F-3 829. T01869 49.1 kDa;Oct-2.8 830. T01930 49.1 kDa; NF-kappaB2 (p49) 831. T02306 49.1 kDa;GCMa 832. T00554 49.2 kDa; NF-1C2 833. T02037 49.3 kDa; ICSBP 834.T01819 49.4 kDa; Pax-6 835. T01870 49.4 kDa; Oct-2.1 836. T00646 49.5kDa; Oct-2.1 837. T00996 49.5 kDa; SRY 838. T01041 49.5 kDa; HSF 839.T01445 49.5 kDa; N-Myc 840. T01864 49.5 kDa; Oct-2.1 841. T02162 49.5kDa; TFIIE-alpha 842. T00053 49.6 kDa; ATF-adelta 843. T00767 49.7 kDa;Sry-delta 844. T00952 49.7 kDa; AP-2 845. T02030 49.7 kDa; Sd 846.T02307 49.7 kDa; GCMa 847. T01341 49.8 kDa; RAR-gamma2 848. T00718 49.9kDa; RAR 849. T00033 50.0 kDa; AP-2 850. T00034 50.0 kDa; AP-2 851.T00037 50.0 kDa; AP-5 852. T00201 50.0 kDa; DTF-1 853. T00222 50.0 kDa;E4F 854. T00380 50.0 kDa; H2RIIBP 855. T00434 50.0 kDa; IUF-1 856.T00435 50.0 kDa; JRF 857. T00479 50.0 kDa; LyF-1 858. T00567 50.0 kDa;NF-E1b 859. T00719 50.0 kDa; RAR-alpha1 860. T00733 50.0 kDa; RPF1 861.T01465 50.0 kDa; TRF (2) 862. T01923 50.0 kDa; NF-kappaB1 863. T0066850.1 kDa; Opaque-2 864. T02053 50.1 kDa; HB24 865. T01260 50.2 kDa; STD1866. T00111 50.3 kDa; c-Ets-1 867. T00721 50.3 kDa; RAR-beta 868. T0132650.3 kDa; RAR-beta2 869. T01330 50.3 kDa; RAR-gamma1 870. T01338 50.3kDa; RAR-beta2 871. T01766 50.3 kDa; MEF-2C (465 AA form) 872. T0204050.3 kDa; c-Ets-1A 873. T00112 50.4 kDa; c-Ets-1 874. T00114 50.4 kDa;c-Ets-1 54 875. T01769 50.4 kDa; MEF-2C 876. T01689 50.5 kDa; Staf-50877. T02292 50.5 kDa; BF-2 878. T00372 50.6 kDa; HNF-4 879. T01056 50.6kDa; slp2 880. T01337 50.6 kDa; RAR-beta1 881. T02144 50.6 kDa; ADA2882. T01335 50.7 kDa; RAR-alpha1 883. T01253 50.8 kDa; PUB1 884. T0134050.8 kDa; RAR-gamma1 885. T01345 50.8 kDa; RXR-alpha 886. T02029 50.8kDa; C/EBP 887. T02051 50.8 kDa; HB24 888. T01333 50.9 kDa; RXR-gamma889. T01336 50.9 kDa; RAR-alpha2 890. T00396 51.0 kDa; Pax-7 891. T0059351.0 kDa; NF-kappaB1 892. T01267 51.0 kDa; GAL80 893. T01390 51.0 kDa;GABP-alpha 894. T01408 51.0 kDa; Fli-1 895. T01906 51.0 kDa; NF-1A5 896.T02066 51.0 kDa; Fli-1 897. T02067 51.0 kDa; Fli-1 898. T00647 51.1 kDa;Oct-2 899. T01815 51.1 kDa; Vab-3 900. T02305 51.1 kDa; MAZi 901. T0065051.2 kDa; Oct-2 902. T01331 51.2 kDa; RXR-alpha 903. T01663 51.2 kDa;TR2-9 904. T02283 51.2 kDa; Kox1 905. T00079 51.3 kDa; Cad 906. T0025151.3 kDa; ELP 907. T00648 51.3 kDa; Oct-2 908. T01402 51.4 kDa;GABP-alpha 909. T01428 51.4 kDa; E4BP4 910. T01572 51.4 kDa; LSIRF-2911. T01831 51.5 kDa; BF-1 912. T01895 51.5 kDa; Pou2 913. T02145 51.5kDa; GCN5 914. T00764 51.6 kDa; SRF 915. T01412 51.6 kDa; NF-EM5 916.T01865 51.8 kDa; Oct-2.3 917. T02246 51.8 kDa; AML1c 918. T01046 51.9kDa; HSF3 919. T00266 52.0 kDa; Erg-2 920. T00394 52.0 kDa; NF-kappaB2921. T00785 52.0 kDa; TAF-I 922. T00899 52.0 kDa; WT1 923. T01074 52.1kDa; Ap 924. T00851 52.2 kDa; T3R-beta 925. T01882 52.3 kDa; Unc-86 926.T02191 52.3 kDa; TFIIH-p50 927. T00694 52.4 kDa; PPAR 928. T00991 52.4kDa; PPAR 929. T01618 52.5 kDa; EBNA-2 930. T00077 52.6 kDa;CACCC-binding factor 931. T00853 52.7 kDa; T3R-beta1 932. T01943 52.7kDa; IkappaBR 933. T02085 52.7 kDa; Elg 934. T02135 52.7 kDa; TAF(I)48935. T01397 52.8 kDa; c-Ets-2 936. T01951 52.8 kDa; HNF-1C 937. T0229752.8 kDa; NF-1A2 938. T01352 52.9 kDa; PPARalpha 939. T01868 52.9 kDa;Oct-2.7 940. T02104 52.9 kDa; HSF1 (short) 941. T00113 53.0 kDa; c-Ets-2942. T00679 53.0 kDa; Pax-3 943. T00680 53.0 kDa; Pax-3 944. T01357 53.0kDa; RAR-gamma1 945. T01417 53.0 kDa; tel 946. T01662 53.0 kDa; TR2 947.T00006 53.2 kDa; Ase 948. T01010 53.2 kDa; RSRFC9 949. T01066 53.3 kDa;runt 950. T01339 53.3 kDa; RAR-beta3 951. T00120 53.5 kDa; CF2-II 952.T01009 53.6 kDa; RSRFC4 953. T01044 53.6 kDa; HSF1 954. T00505 53.7 kDa;MEF-2 955. T01933 53.8 kDa; Cactus 956. T02008 53.8 kDa; Ems 957. T0212953.8 kDa; p55erg 958. T02130 53.8 kDa; p49erg 959. T01200 53.9 kDa;Egr-1 960. T02041 53.9 kDa; c-Ets-2A 961. T02127 53.9 kDa; c-Ets-2B 962.T00220 54.0 kDa; E2F 963. T00221 54.0 kDa; E2F 964. T00373 54.0 kDa;HNF-4 965. T01354 54.1 kDa; PPARgamma 966. T01771 54.1 kDa; MEF-2D 967.T00894 54.3 kDa; Vmw65 968. T01054 54.3 kDa; Fkh 969. T01772 54.3 kDa;D-MEF2 970. T00599 54.4 kDa; NF-1/L 971. T01517 54.4 kDa; Twi 972.T01571 54.4 kDa; IRF-3 973. T00063 54.5 kDa; Bcd 974. T00116 54.5 kDa;c-Ets-2 58-64 975. T00167 54.5 kDa; CRE-BP1 976. T02291 54.5 kDa; Croc977. T01905 54.6 kDa; NF-1A4 978. T01713 54.7 kDa; HOXA10 979. T0191754.7 kDa; NF-1X3 980. T02239 54.7 kDa; TFIIE-alpha 981. T00301 54.8 kDa;GAGA factor 982. T01005 54.8 kDa; MEF-2 983. T01153 54.8 kDa; T3R-alpha2984. T00384 54.9 kDa; HSF 985. T01525 54.9 kDa; HSF1 986. T00115 55.0kDa; c-Ets-1 68 987. T00117 55.0 kDa; CF1 988. T00314 55.0 kDa; GATA-3989. T01198 55.0 kDa; NRF-2 990. T01199 55.0 kDa; NRF-2 991. T01240 55.0kDa; ABF1 992. T01349 55.0 kDa; RXR-beta 993. T01362 55.0 kDa; Hp55 994.T01476 55.0 kDa; Abd-B 995. T01343 55.1 kDa; T3R-alpha2 996. T01910 55.1kDa; NF-1B3 997. T01918 55.1 kDa; NF-1C1 998. T02281 55.1 kDa; AML3 999.T01084 55.2 kDa; TEC1 1000. T01875 55.4 kDa; Oct-2 1001. T00175 55.5kDa; CTF-1 1002. T01901 55.5 kDa; PDM-2 1003. T00176 55.6 kDa; CTF-11004. T01616 55.7 kDa; RBP-Jkappa 1005. T01062 55.8 kDa; PEBP2alphaA11006. T00897 55.9 kDa; v-Rel 1007. T01770 55.9 kDa; MEF-2D 1008. T0030756.0 kDa; GATA-2 1009. T00509 56.0 kDa; MIG1 1010. T00692 56.0 kDa; PO-B1011. T00993 56.0 kDa; hsp56 1012. T01226 56.0 kDa; PO-B 1013. T0190456.0 kDa; NF-1A1.1 1014. T02296 56.0 kDa; NF-1A1 1015. T01853 56.1 kDa;SOX-9 1016. T02308 56.1 kDa; GCMb 1017. T01597 56.2 kDa; NF2d9 1018.T02302 56.2 kDa; GCM 1019. T01907 56.3 kDa; NF-1C1 1020. T01784 56.4kDa; MEF-2 1021. T01603 56.5 kDa; dCREB-A 1022. T00244 56.6 kDa; Egr-11023. T01941 56.6 kDa; IkappaB-gamma1 1024. T01308 56.8 kDa; CRE-BPa1025. T01334 56.9 kDa; RXR-beta 1026. T00152 57.0 kDa; CP2 1027. T0080757.0 kDa; TEF-2 1028. T00151 57.2 kDa; CP2 1029. T01998 57.2 kDa; Cnc1030. T01042 57.3 kDa; HSF1 (long) 1031. T01568 57.3 kDa; MYB.Ph3 1032.T00956 57.4 kDa; DSXM 1033. T02318 57.4 kDa; PEBP2alphaA/til-1 1034.T00544 57.5 kDa; NF-1A1 1035. T01088 57.7 kDa; ILF 1036. T01273 57.9kDa; TAF(II)60 1037. T01950 57.9 kDa; HNF-1B 1038. T00058 58.0 kDa; BAP1039. T00389 58.0 kDa; H2TF1 1040. T00440 58.0 kDa; KBF2 1041. T0136458.0 kDa; p58 1042. T02164 58.0 kDa; TFIIE 1043. T01350 58.1 kDa;T3R-beta2 1044. T00972 58.2 kDa; HSF2 1045. T02168 58.3 kDa; TFIIF-alpha1046. T01953 58.4 kDa; vHNF-1B 1047. T01617 58.5 kDa; RBP-Jkappa 1048.T01909 58.6 kDa; NF-1B2 1049. T02171 58.7 kDa; TFIIF-alpha 1050. T0232058.7 kDa; PEBP2alphaA/til-1 (Y) 1051. T00358 59.0 kDa; HEF-1T 1052.T00990 59.0 kDa; FKBP59 1053. T01527 59.0 kDa; RORalpha1 1054. T0189759.0 kDa; Cf1a 1055. T01523 59.1 kDa; p65delta 1056. T01934 59.1 kDa;c-Rel 1057. T00253 59.4 kDa; En 1058. T01883 59.5 kDa; CEH-18 1059.T00252 60.0 kDa; embryo DNA binding protein 1060. T00448 60.0 kDa; 60Kprotein 1061. T00553 60.0 kDa; NF-BA1 1062. T00608 60.0 kDa; NF-W1 1063.T00622 60.0 kDa; NHP-2 1064. T00649 60.0 kDa; Oct-2 1065. T00734 60.0kDa; RVF 1066. T00735 60.0 kDa; RVF 1067. T00736 60.0 kDa; RVF 1068.T00812 60.0 kDa; TFEB 1069. T00884 60.0 kDa; VDR 1070. T00906 60.0 kDa;XPF-1 1071. T01133 60.0 kDa; TTF-2 1072. T01195 60.0 kDa; NHP-2 1073.T01196 60.0 kDa; NHP-2 1074. T01489 60.0 kDa; RBP60 1075. T01490 60.0kDa; RBP60 1076. T02167 60.0 kDa; TFIIE 1077. T00594 60.2 kDa; RelA1078. T00595 60.2 kDa; RelA 1079. T00964 60.2 kDa; Oct-2B 1080. T0104360.3 kDa; HSF2 1081. T01932 60.3 kDa; RelB 1082. T00676 60.6 kDa; Pap1+1083. T01614 60.6 kDa; Skn-1 1084. T00684 60.8 kDa; PEA3 1085. T0026361.0 kDa; ER 1086. T02154 61.2 kDa; SRB10 1087. T00891 61.3 kDa; vHNF-1A1088. T00889 61.4 kDa; vHNF-1 1089. T01955 61.5 kDa; vHNF-1 1090. T0089061.7 kDa; vHNF-1 1091. T00918 61.8 kDa; Zeste 1092. T02282 61.8 kDa;Glass 1093. T00289 62.0 kDa; f-EBP 1094. T00351 62.0 kDa; HAP4 1095.T00449 62.0 kDa; 62K protein 1096. T00604 62.0 kDa; NF-1/Red1 1097.T00936 62.0 kDa; ENKTF-1 1098. T01070 62.0 kDa; TREF2 1099. T01399 62.0kDa; TCF 1100. T01931 62.0 kDa; RelB 1101. T02183 62.0 kDa; TFIIH-p621102. T01040 62.1 kDa; Olf-1 1103. T01529 62.3 kDa; RORalpha3 1104.T00329 62.5 kDa; Glass 1105. T00551 62.6 kDa; NF-1B1 1106. T01045 62.8kDa; HSF2 1107. T01997 62.8 kDa; dFRA 1108. T00474 63.0 kDa; LSF 1109.T00803 63.0 kDa; TCF-2alpha 1110. T00862 63.0 kDa; UBP-1 1111. T0124663.0 kDa; TBF1 1112. T01528 63.0 kDa; RORalpha2 1113. T02134 63.0 kDa;TAF(I)63 1114. T01894 63.1 kDa; pou[c] 1115. T00689 63.4 kDa; PHO2 1116.T01256 63.6 kDa; HCM1 1117. T02248 63.6 kDa; StuAp 1118. T00193 63.8kDa; Dfd 1119. T00095 64.0 kDa; CCAAT-binding factor 1120. T00701 64.0kDa; PTF1-beta 1121. T01185 64.0 kDa; CCAAT-binding factor 1122. T0118664.0 kDa; CCAAT-binding factor 1123. T01227 64.0 kDa; PTF1 1124. T0125464.3 kDa; PAB1 1125. T02124 64.3 kDa; TAF(II)60 1126. T01112 64.4 kDa;EBF 1127. T02173 64.5 kDa; TFIIF-alpha 1128. T01940 64.8 kDa;IkappaB-gamma 1129. T00169 65.0 kDa; c-Rel 1130. T00262 65.0 kDa; ER1131. T00392 65.0 kDa; H4TF-2 1132. T00560 65.0 kDa; NF-E4 1133. T0058765.0 kDa; NF-kappaB 1134. T00588 65.0 kDa; NF-kappaB 1135. T00590 65.0kDa; NF-kappaB 1136. T01363 65.0 kDa; Hp65 1137. T02247 65.0 kDa; Staf1138. T01900 65.2 kDa; PDM-1 1139. T02266 65.2 kDa; PEBP2alphaA/Osf21140. T01598 65.3 kDa; ECH 1141. T01672 65.3 kDa; RFX5 1142. T00699 65.5kDa; Prd 1143. T00049 66.0 kDa; ATF 1144. T00062 66.0 kDa; BGP1 1145.T00156 66.0 kDa; alpha-CP2a, alpha-CP2b 1146. T01443 66.1 kDa; Nrf21147. T00261 66.2 kDa; ER 1148. T00463 66.3 kDa; Lc 1149. T00674 66.4kDa; E47 1150. T00710 66.6 kDa; R 1151. T00264 66.7 kDa; ER 1152. T0115466.8 kDa; c-Rel 1153. T01415 66.8 kDa; pointedP1 1154. T01615 66.9 kDa;Su(H) 1155. T02204 66.9 kDa; Nrf2 1156. T00258 67.0 kDa; ER 1157. T0025967.0 kDa; ER 1158. T00672 67.0 kDa; p67 1159. T00761 67.0 kDa; SRF 1160.T00762 67.0 kDa; SRF 1161. T00765 67.0 kDa; SRF 1162. T01244 67.0 kDa;HSF 1163. T02272 67.0 kDa; HEB1-p67 1164. T01211 67.2 kDa; HNF-1 1165.T00207 67.3 kDa; E47 1166. T00368 67.3 kDa; HNF-1A 1167. T01664 67.3kDa; TR2-11 1168. T00204 67.4 kDa; E12 1169. T01113 67.5 kDa; Elf-11170. T00675 67.7 kDa; E12 1171. T01849 67.9 kDa; Ixr1 1172. T02287 67.9kDa; phiAP3 1173. T00203 68.0 kDa; E1 1174. T00791 68.0 kDa; TAR factor1175. T01245 68.0 kDa; Reb1p 1176. T01374 68.0 kDa; URF 1177. T0210068.1 kDa; Zeste 1178. T02064 68.2 kDa; Lab 1179. T00168 68.5 kDa; c-Rel1180. T01292 68.6 kDa; RIM1 1181. T00843 69.0 kDa; Ttk 69K 1182. T0183569.2 kDa; Whn 1183. T01952 69.2 kDa; HNF-1 1184. T01258 69.7 kDa; MSN41185. T02078 69.7 kDa; Otd 1186. T00068 70.0 kDa; BRF1 1187. T00621 70.0kDa; NHP-1 1188. T01165 70.0 kDa; H16 1189. T01193 70.0 kDa; NHP-1 1190.T01194 70.0 kDa; NHP-1 1191. T01787 70.0 kDa; E12 1192. T01306 70.2 kDa;SKO1 1193. T01250 70.3 kDa; BUF2 1194. T02310 70.3 kDa; MET4 1195.T01793 70.4 kDa; GE1 1196. T00433 71.2 kDa; ITF-2 1197. T00138 71.5 kDa;c-Myb 1198. T02208 71.5 kDa; TAF(II)70-gamma 1199. T01660 71.8 kDa; PR A1200. T00976 72.0 kDa; NFdeltaE3A 1201. T00028 72.5 kDa; AP-1 1202.T00137 72.5 kDa; c-Myb 1203. T00139 72.5 kDa; c-Myb 1204. T00783 72.7kDa; TAF(II)70-alpha 1205. T01497 72.9 kDa; ALF1A 1206. T01503 72.9 kDa;HEB 1207. T01679 72.9 kDa; PacC 1208. T01789 72.9 kDa; SCBPgamma 1209.T02190 72.9 kDa; TFIIH-p73 1210. T00064 73.0 kDa; BmFTZ-F1 1211. T0088773.0 kDa; VETF 1212. T01863 73.0 kDa; Oct-1C 1213. T01087 73.3 kDa; Vp11214. T01783 73.5 kDa; RLM1 1215. T00750 73.6 kDa; Sim 1216. T01251 73.7kDa; PCT1 1217. T01994 73.7 kDa; CAUP 1218. T01034 73.9 kDa; Da 1219.T00219 74.0 kDa; E2F 1220. T00495 74.0 kDa; MBF-I 1221. T01594 74.7 kDa;v-Myb/v-Ets 1222. T00054 75.0 kDa; ATF-like 1223. T00136 75.0 kDa; c-Myb1224. T00443 75.0 kDa; 75 kDa protein 1225. T00662 75.0 kDa; Oct-2B1226. T01421 75.0 kDa; PTF1-alpha 1227. T01264 75.4 kDa; HST 1228.T01993 75.4 kDa; ARA 1229. T00196 75.5 kDa; Dl 1230. T01791 75.7 kDa;SCBPbeta 1231. T01496 75.8 kDa; ALF1B 1232. T01790 75.8 kDa; SCBPalpha1233. T01289 75.9 kDa; STE12 1234. T00855 76.0 kDa; TSAP 1235. T0103176.0 kDa; Oct-1 1236. T00641 76.5 kDa; Oct-1 1237. T01669 76.5 kDa; RFX21238. T01862 76.8 kDa; Oct-1B 1239. T00386 76.9 kDa; HSTF 1240. T0141677.6 kDa; pointedP2 1241. T01586 77.7 kDa; B-Myb 1242. T01257 77.8 kDa;MSN2 1243. T01945 77.8 kDa; NF-ATc 1244. T02209 77.9 kDa; TAF(II)70-beta1245. T00772 78.0 kDa; STE12 1246. T02148 78.5 kDa; SRB4 1247. T0139678.6 kDa; yan 1248. T00065 78.8 kDa; B-Myb 1249. T02322 78.8 kDa; BCL-61250. T00922 79.1 kDa; Zmhox1a 1251. T01587 79.1 kDa; B-Myb 1252. T0031579.3 kDa; GBF 1253. T02122 79.3 kDa; TAF(II)80 1254. T02146 79.3 kDa;ADA3 1255. T01670 79.4 kDa; RFX3 1256. T00644 79.5 kDa; Oct-1A 1257.T01097 79.5 kDa; GT-2 1258. T01975 79.9 kDa; RREB-1 1259. T00211 80.0kDa; EBNA-1 1260. T01161 80.0 kDa; EBP-80 1261. T01667 80.0 kDa; RFX21262. T01856 80.7 kDa; SSRP1 1263. T00754 81.0 kDa; Sp1 1264. T0100381.1 kDa; SSRP1 1265. T01442 81.5 kDa; Nrf1 1266. T01920 81.5 kDa; GRbeta 1267. T02203 81.5 kDa; Nrf1 1268. T01848 81.7 kDa; Dm-SSRP1 1269.T02278 81.7 kDa; SEM-4 1270. T00056 82.0 kDa; BAF1 1271. T00451 82.0kDa; 77 + 82K protein 1272. T01069 82.0 kDa; TREF1 1273. T02175 82.2kDa; TFIIF-alpha 1274. T01661 82.4 kDa; PR A 1275. T00172 82.8 kDa; CTCF1276. T02284 82.8 kDa; CTCF 1277. T00383 83.0 kDa; HSF 1278. T01573 83.0kDa; STAT1beta 1279. T02315 83.1 kDa; Rc 1280. T01454 83.2 kDa; Hsp901281. T01585 83.6 kDa; A-Myb 1282. T02285 83.7 kDa; CTCF 1283. T0179484.0 kDa; INSAF 1284. T00426 85.0 kDa; alpha-IRP 1285. T00867 85.0 kDa;UHF-1 1286. T01295 85.0 kDa; FTS 1287. T01796 85.0 kDa; Arnt (774 AAform) 1288. T01583 85.1 kDa; A-Myb 1289. T01845 85.2 kDa; Sox-LZ 1290.T01252 85.5 kDa; CDC10 1291. T01584 85.5 kDa; A-Myb 1292. T02084 85.6kDa; Pb 1293. T02219 85.6 kDa; Lz 1294. T00337 85.7 kDa; GR alpha 1295.T00698 85.7 kDa; PR 1296. T00931 85.8 kDa; AmdR 1297. T01576 85.9 kDa;STAT4 1298. T00914 86.0 kDa; YPF1 1299. T01582 86.0 kDa; A-Myb 1300.T00335 86.1 kDa; GR 1301. T01988 86.4 kDa; STAT 1302. T00002 86.6 kDa;ACE2 1303. T01346 86.6 kDa; Arnt 1304. T00784 86.7 kDa; TAF(II)100 1305.T01684 86.9 kDa; TEA1 1306. T02182 86.9 kDa; TFIIH-p80 1307. T01797 87.0kDa; Arnt 1308. T00208 87.1 kDa; E74A 1309. T01575 87.2 kDa; STAT1 1310.T01844 87.2 kDa; Sox-LZ 1311. T02177 87.2 kDa; SIII-p110 1312. T0217887.2 kDa; SIII-p110 1313. T01492 87.3 kDa; STAT1alpha 1314. T01642 87.3kDa; NUC-1 1315. T01547 87.5 kDa; dE2F 1316. T00455 88.0 kDa; Krox-241317. T00929 88.0 kDa; PRDI-BF1 1318. T01574 88.0 kDa; STAT3 1319.T01493 88.1 kDa; STAT3 1320. T00844 88.2 kDa; Ttk 88K 1321. T00709 89.0kDa; qa-1F 1322. T01085 89.2 kDa; abaA 1323. T02181 89.3 kDa; TFIIH-p901324. T02189 89.8 kDa; TFIIH-p85 1325. T00055 90.0 kDa; B‘’ 1326. T0036990.0 kDa; HNF-1 1327. T00387 90.0 kDa; H1TF1 1328. T00638 90.0 kDa; NTF1329. T00944 90.0 kDa; STAT5B 1330. T00992 90.0 kDa; Hsp90 1331. T0127290.0 kDa; TAF-90 1332. T02243 90.0 kDa; TFIIF 1333. T01013 90.6 kDa;SWI6 1334. T01579 90.8 kDa; STAT5A 1335. T01578 90.9 kDa; STAT5 1336.T00320 91.0 kDa; GCF 1337. T01247 91.0 kDa; UME6 1338. T01795 91.7 kDa;AhR 1339. T00725 92.1 kDa; REB1 1340. T00715 92.5 kDa; RAP1 1341. T0161092.7 kDa; HIF-1alpha 1342. T00385 93.3 kDa; HSTF 1343. T01818 93.3 kDa;Ey 1344. T01581 93.7 kDa; STAT6 1345. T00333 94.0 kDa; GR 1346. T0161194.0 kDa; HIF-1beta 1347. T02271 94.0 kDa; HEB1-p94 1348. T00940 94.1kDa; GRF-1 1349. T01580 94.1 kDa; STAT6 1350. T00322 94.3 kDa; GCR11351. T00957 94.3 kDa; OBP 1352. T00210 94.8 kDa; E74B 1353. T00018 95.0kDa; AhR 1354. T00739 95.0 kDa; SBF-1 1355. T00759 95.0 kDa; Sp1 1356.T01230 95.0 kDa; Vav 1357. T02133 95.3 kDa; TAF(I)110 1358. T02192 95.3kDa; TFIIH-SSL2/RAD25 1359. T00768 95.4 kDa; Sry h-1 1360. T02316 95.8kDa; Blimp-1 1361. T00453 96.0 kDa; 96K-protein 1362. T00019 96.2 kDa;AhR 1363. T00458 97.0 kDa; LAC9 1364. T00779 97.0 kDa; TAF(II)125 1365.T01494 97.9 kDa; STAT2 1366. T00041 98.2 kDa; AR 1367. T00042 98.2 kDa;AR 1368. T00880 98.4 kDa; Vav 1369. T01562 98.5 kDa; ADD1 1370. T0069798.7 kDa; PR 1371. T00040 99.0 kDa; AR 1372. T00302 99.0 kDa; GAL4 1373.T00696 99.0 kDa; PR 1374. T02121 99.3 kDa; TAF(II)110 1375. T01929 99.7kDa; NF-kappaB2 precursor 1376. T00194 100.0 kDa; dioxin receptor 1377.T00642 100.0 kDa; Oct-1 1378. T00788 100.0 kDa; T-Ag 1379. T01305 100.0kDa; CBP100 1380. T01927 100.6 kDa; NF-kappaB2 precursor 1381. T01499102.0 kDa; IL-6 RE-BP 1382. T01666 103.7 kDa; RFX1 1383. T01673 104.7kDa; RFX1 1384. T01109 105.0 kDa; TCF-1 1385. T01925 105.4 kDa;NF-kappaB1 precursor 1386. T01924 105.6 kDa; NF-kappaB1 precursor 1387.T01486 106.1 kDa; p107 1388. T00805 106.2 kDa; Tsh 1389. T00774 106.3kDa; su(Hw) 1390. T00511 106.6 kDa; MR 1391. T00513 106.9 kDa; MR 1392.T00970 108.0 kDa; MEP-1 1393. T00161 110.0 kDa; CPE binding protein1394. T00296 110.0 kDa; FTZ-F1 1395. T00391 110.0 kDa; H4TF-1 1396.T00420 110.0 kDa; IRBP 1397. T01271 110.0 kDa; TAF(II)110 1398. T00669110.6 kDa; Ovo 1399. T01558 111.1 kDa; SREBP-1c 1400. T01163 111.4 kDa;PUT3 1401. T02143 112.8 kDa; TIF1 1402. T00428 113.0 kDa; ISGF-3 1403.T01243 113.0 kDa; TSF3 1404. T01455 113.0 kDa; ISGF-3alpha 1405. T02034113.4 kDa; SWI4 1406. T01557 113.5 kDa; SREBP-1b 1407. T00086 114.1 kDa;CBF (5) 1408. T02314 114.2 kDa; BZP 1409. T00502 115.0 kDa; MEB-1 1410.T00503 115.0 kDa; MEB-1 1411. T01946 115.6 kDa; NF-ATx 1412. T01019116.0 kDa; Elf-1 1413. T02244 116.0 kDa; TFIIF 1414. T02215 116.7 kDa;TIF1 (1051 AA form) 1415. T00273 117.0 kDa; Evi-1 1416. T00919 117.4kDa; Zfh-1 1417. T00330 118.0 kDa; GLI 1418. T00270 120.0 kDa; ETF 1419.T01379 120.0 kDa; 120-kDa CRE-binding protein 1420. T01944 120.0 kDa;NF-ATp 1421. T01948 120.0 kDa; NF-ATp 1422. T01559 120.5 kDa; SREBP-11423. T01270 120.7 kDa; TAF(II)145 1424. T01556 121.6 kDa; SREBP-1a1425. T00842 122.8 kDa; Tra-1 (long form) 1426. T01467 123.1 kDa;deltaEF1 1427. T01694 123.1 kDa; NF-X1 1428. T00835 123.2 kDa; TMF 1429.T01688 123.3 kDa; STC 1430. T01560 123.7 kDa; SREBP-2 1431. T01561 123.7kDa; SREBP-2 1432. T00775 123.8 kDa; SWI4 1433. T00625 124.1 kDa; AREB61434. T01608 128.4 kDa; p130 1435. T00879 130.0 kDa; vaccinia virusDNA-binding protein 1436. T01367 133.0 kDa; E75A 1437. T02120 138.5 kDa;TAF(II)150 1438. T01077 140.0 kDa; c-abl 1439. T02152 143.8 kDa; SRB81440. T02042 144.3 kDa; Cux 1441. T00778 147.0 kDa; TAF 1442. T00382150.0 kDa; HSE-binding protein 1443. T00011 151.0 kDa; ADR1 1444. T01368152.0 kDa; E75B 1445. T02153 160.0 kDa; SRB9 1446. T01269 161.5 kDa;TAF(II)150 1447. T02286 162.2 kDa; MTB-Zf 1448. T00346 164.0 kDa; HAP11449. T00100 164.4 kDa; CDP 1450. T00401 170.0 kDa; ICP4 1451. T01268170.0 kDa; TAF(II)170 1452. T00331 172.0 kDa; GLI3 1453. T00366 180.0kDa; HIP1 1454. T01377 180.0 kDa; E2F-BF 1455. T01682 180.0 kDa;PTFalpha 1456. T01261 180.8 kDa; brahma 1457. T02207 189.4 kDa;TAF(II)250Delta 1458. T01949 190.0 kDa; NF-ATc3 1459. T00473 200.0 kDa;LIT-1 1460. T02206 212.7 kDa; CCG1 1461. T00096 214.4 kDa; CCBF 1462.T00781 214.7 kDa; TAF(II)250 1463. T01038 220.0 kDa; TFIIF 1464. T01378220.0 kDa; E2F-I 1465. T00822 230.0 kDa; TFIIE 1466. T02262 230.0 kDa;TFIIH 1467. T02119 232.5 kDa; TAF(II)250 1468. T02004 233.6 kDa; Cut1469. T02317 243.7 kDa; Zn-15 1470. T01427 264.1 kDa; p300 1471. T02214265.1 kDa; CBP 1472. T01318 265.5 kDa; CBP 1473. T02313 267.4 kDa; MIBP11474. T00939 274.9 kDa; HIV-EP2 1475. T00007 288.3 kDa; alphaA-CRYBP11476. T00497 297.0 kDa; MBP-1 (1) 1477. T00071 300.0 kDa; B-TFIID 1478.T02107 300.0 kDa; PC5 1479. T00048 305.7 kDa; ATBF1-B 1480. T00920 332.1kDa; Zfh-2 1481. T00850 404.0 kDa; Ttx 1482. T01665 404.5 kDa; ATBF1-A1483. T02140 500.0 kDa; PC2

TABLE 4 Selected examples of RS-related proteins identified from thedatabase searches, sorted according to cluster assignment and functionalassociation. ¹ Motifs Name of Functional Entry Cluster (other protein/association number number Species than RS) homolog Splicing (RS- 3 2 DmSRM300 related 4 3 Ce SWAP2 5 3 Dm SWAP2 6 4 Hs SWAP2 9 6 Hs SIP1 23 7Hs RRM RNPS1 35 7, 64 Dm RRM U1-70K 38 7, 64, 110, Dm RRM U2AF-50 127,131, 141 SWISS-PROT: U2AF-65 P26368 SWISS-PROT: 9G8 Q16629 44 7, 64,127, 141 Ce RRM U1-70K 76 21 Dm SURP SWAP1 89 28 Dm KH- SF1 RBD/ZNF 9029 Dm PWI SRM16O 101 38 Dm TRA 111 46 Ce DEAD- U5-100K BOX 114 46 DmDEAD- U5-100K BOX 115 47 Ce DEAD- HRH1 BOX 116 47 Dm S1- HRH1 RBD/DEAH-BOX 244 120 Dm RRM TRA2 SWISS-PROT: U1 snRNP 70 kDa P08621 SWISS-PROT:U2AF 35 kDa Q01081 SWISS-PROT: U2AF 65 kDa P26368 ENSP00000261905, U5snRNP 100 kDa Q9BUQ8 SWISS-PROT: SC35 Q01130 SWISS-PROT: SRp20 P23152SWISS-PROT: SRp30C Q13242 SWISS-PROT: SRp54 Q05519 SWISS-PROT: SRp55Q13247 SWISS-PROT: SF2 Q07955 SWISS-PROT: DEAH-box protein 8 Q14562SWISS-PROT: hnRNP G P38159 SWISS-PROT: Serine/tbreonine- Q13523 proteinkinase SWISS-PROT: Hypothetical protein Q9Y388 CGI-79.B SWISS-PROT:B-lymphocyte Q02040 antigen precursor 3′-end processing 97 36 Ce FIP1 9836 Dm FF FIP1 119 50 Ce CF-IM 68K 120 50 Dm CF-IM 68K Chrornatin- 108 44Dm CIR associated 190 87 Hs RRM ACINUS 191 87 Dm (RRM) ACINUS 212 103 DmBROMO GCN5 Transcription 11 6 Dm PHD/ZNF/ SCAF1 (RNA pol II- RINGassociated 17 7 Hs SCAF4 25 7, 17 Hs SCAF10/SR-CYP 30 7, 17, 64, 127, DmRRM SCAF8 131 63 16 Hs SCAF9 75 20 Ce SRP129/SCAF11 82 25 Ce ZNF/RING/FCP1a PHOS 99 36 Dm WW CA150 164 69 Ce CYCLIN CYCLIN L 165 69 Dm CYCLINCYCLIN L 249 124 Dm DSLF-P160/SPT5 Transcription 24 7, 17, 64, 127 HsLISCH (other) 85 27 Hs CACTIN1 87 27 Dm CACTIN1 133 60 Dm ZNF/RING NF-X1/SHUTTLECRAFT 208 100 Hs BTF 291 137 Dm PHD ALHAMBRA Kinases and 20399 Hs KIN PRP4-RELATED phosphatases KINASE 204 99 Hs KIN CLK-2 KINASE206 99 Dm KIN PITSLRE KINASE 207 99 Dm KIN CRK7 KINASE 320 148 Sc RHODPpz1p 324 152 Sc PHOS Mip1p/Cdc25p Cell structure 168 72 Hs B41 BAND 4 +1-LIKE 169 72 Dm B41 BAND 4 + 1-LIKE 235 114 Sc Sla1p

TABLE 5 Oligonucleotide sequences used for ChIP PCR and Real Time PCRanalysis. Amplicon Forward Primer Reverse Primer HIV LTR ctgcatccggagtacaaccagagaagaccc ttcaagaac agtacaggc FFL atgtatagatttgaa gataaatcgtatttggaagagctgtttct tcaatcagagtgct gapdh tactagcggttttac tcgaacaggaggagcgggcg agagagcga hsp70 gaagagtctggagag ccttttcccttctga ttctg gccaap21/CIP tatatcagggccgcg ggctccacaaggaac ctg tgacttc cad atcccgtggctccgcgcaaactccactgga ggac accac HLA-DRA aacccttcccctagc ctagcacagggactcaacagat cacttatg Antibodies used in the IP and ChIP assays. SourceCatalog Protein (Company) Number GFP Santa Cruz sc-8334 BiotechnologiesRNA Polymerase Santa Cruz sc-899 II (N20) Biotechnologies CTD (8WG16)Covance MMS-126R S5P-CTD (H14) Covance MMS134R S2P-CTD (H5) CovanceMMS-129R HA Covance MMS-101P CyclinT1 Santa Cruz sc-10750Biotechnologies Normal Rabbit IgG Upstate 12-370 HIV Tat CovanceMMS-116P Nucleolin Santa Cruz sc-13057

1. A method of regulating transcription of a gene, the method comprisingthe step of: expressing in a cell a nucleic acid construct in an amountsufficient for modulation of transcription, the construct comprising afirst nucleic acid sequence encoding a transcription factor protein or afragment thereof linked to a second nucleic acid sequence encoding aprotein or a fragment thereof that localizes to the transcriptionalmachinery.
 2. The method of claim 1, wherein the transcription factorprotein is selected from the group consisting of: viral transcriptionfactors, nuclear proto-oncogene or oncogene proteins, nuclear tumorsuppressor proteins, heart specific transcription factors, and immunesystem transcription factors.
 3. The method of claim 2, wherein theviral transcription factor is selected from the group consisting ofHIV-Tat, HPV-E2, HPV-E7, BPV-E2, Adenovirus IVa2, HSV-1 ICP4, EBNA-LP,EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C, BZLF-1, CMV-IE-1, CMV-1E2, HHSV-8 KbZIP, HBV Hbx, Poxvirus Vaccinia, VETF, HCV NS5A, T-Ag, Adenovirus E1A,Herpesvirus VP16, HTLV Tax, Hepadnavirus X protein, and BaculovirusAcNPV IE-1.
 4. The method of claim 2, wherein the nuclear proto-oncogeneor oncogene protein is selected from the group consisting of: Ab1, Myc,Myb, Re1, Jun, Fos, Sp1, Ap1, NF-κB, STAT 3 or 5, β-catenin, Notch, GLI,and PML-RARα.
 5. The method of claim 2, wherein the heart specifictranscription factor is selected from the group consisting of: Nkx 2, 3,4, or 5, TBX5, GATA 4, 5, or 6, and MEF2.
 6. The method of claim 2,wherein the immune cell specific transcription factor is selected fromthe group consisting of: Ikaros, PU.1, PAX-5, Oct-2, and BOB.1/OBF.1. 7.The method of claim 1, wherein the transcription factor protein orfragment thereof is a dominant negative transcription factor.
 8. Themethod of claim 1, wherein the transcription factor protein or fragmentthereof is an activation domain (AD) fragment of the transcriptionfactor.
 9. The method of claim 1, wherein the transcription factorprotein or a fragment thereof is Tat.
 10. The method of claim 1, whereinthe transcription factor protein or fragment thereof is Tat activationdomain (Tat AD).
 11. The method of claim 1, wherein the protein or afragment thereof that localizes to the transcriptional machinery isselected from the group consisting of: a protein with nuclearlocalization, a component of the transcriptional machinery, and aprotein that functions in co-transcriptional processing of RNA.
 12. Themethod of claim 11, wherein the protein that functions inco-transcriptional processing of RNA is selected from the groupconsisting of: a capping factor, a splicing factor, a polyadenylationfactor, an RNA export factor, and a translation factor.
 13. The methodof claim 12, wherein the splicing factor is an RS domain containingprotein.
 14. The method of claim 11, wherein the splicing factor isSF-1.
 15. The method of claim 11, wherein the splicing factor is U2AF65.16. The method of claim 11, wherein the splicing factor is 9G8.
 17. Themethod of claim 11, wherein the polyadenylation factor is CstF1
 18. Themethod of claim 1, wherein the transcription factor protein or afragment thereof is a transcriptional activator.
 19. The method of claim1, wherein the transcription factor protein or a fragment thereof is atranscriptional repressor.
 20. The method of claim 1, wherein themodulation of transcription is inhibition of transcription.
 21. Themethod of claim 20, wherein the inhibition of transcription is at least25%.
 22. The method of claim 20, wherein the inhibition of transcriptionis at least 50%.
 23. The method of claim 20, wherein the inhibition oftranscription is at least 75%.
 24. The method of claim 20, wherein theinhibition of transcription is at least 95%.
 25. The method of claim 1,wherein the modulation of transcription is by inhibition oftranscriptional initiation.
 26. The method of claim 1, wherein themodulation of transcription is by inhibition of transcriptionalelongation.
 27. The method of claim 1, wherein the modulation oftranscription is by inhibition of transcriptional termination.
 28. Themethod of claim 1, wherein the modulation of transcription is activationof transcription.
 29. The method of claim 1, wherein the cell is aT-cell infected with an immunodeficiency virus.
 30. The method of claim29, wherein the immunodeficiency virus is HIV.
 31. The method of claim29, wherein the immunodeficiency virus is selected from the groupconsisting of FIV, BIV, and SIV.
 32. The method of claim 1, wherein thecell is selected from the group consisting of a cancer cell, heart cell,or immune system cell.
 33. The method of claim 32, wherein the cancercell is selected from the group consisting of: carcinomas, sarcomas,adenocarcinomas, lymphomas, leukemias, solid tumors of the kidney,breast, lung, bladder, colon, ovarian, prostate, pancreas, stomach,brain, head and neck, skin, uterine, testicular, glioma, esophagus, andliver.
 34. The method of claim 32, wherein the immune system cell isselected from the group consisting of B-cells, T-cells, macrophages,dendritic cells.
 35. A vector comprising the nucleic acid construct ofclaim
 1. 36. A cell comprising the nucleic acid construct of claim 1.37. A protein comprising the amino sequence encoded by the nucleic acidconstruct of claim
 1. 38. A composition comprising the nucleic acidconstruct of claim 1 and a physiologically acceptable carrier.
 39. Acomposition comprising the protein of claim 37 and a physiologicallyacceptable carrier.
 40. A method of regulating transcription of a gene,the method comprising the steps of expressing in a cell a nucleic acidconstruct in an amount sufficient for modulation of transcription, theconstruct comprising a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a splicing factor or a fragment thereof.41. The method of claim 40, wherein the transcription factor protein isselected from the group consisting of viral transcription factors,nuclear proto-oncogenes or oncogenes, heart specific transcriptionfactors, and immune system transcription factors.
 42. The method ofclaim 40, wherein the transcription factor protein or a fragment thereofis Tat.
 43. The method of claim 40, wherein the transcription factorprotein or fragment thereof is an activation domain (AD) fragment of thetranscription factor.
 44. The method of claim 40, wherein thetranscription factor protein or fragment thereof is Tat activationdomain (Tat AD).
 45. The method of claim 40, wherein the splicing factoris a protein containing an RS domain or a fragment thereof.
 46. Themethod of claim 40, wherein the splicing factor is SF1.
 47. The methodof claim 40, wherein the splicing factor is U2AF65.
 48. The method ofclaim 40, wherein the splicing factor is 9G8.
 49. A method of inhibitingreplication of an immunodeficiency virus, the method comprising thesteps of expressing in a cell a nucleic acid construct in an amountsufficient for modulation of viral transcription, the constructcomprising a first nucleic acid sequence encoding a transcription factorprotein or a fragment thereof linked to a second nucleic acid sequenceencoding a protein or a fragment thereof that localizes to thetranscriptional machinery.
 50. A method of inhibiting replication of animmunodeficiency virus, the method comprising the steps of expressing ina cell a nucleic acid construct in an amount sufficient for modulationof viral transcription, the construct comprising a first nucleic acidsequence encoding a Tat protein or a fragment thereof linked to a secondnucleic acid sequence encoding a protein or a fragment thereof thatlocalizes to the transcriptional machinery.
 51. A method of inhibitingreplication of an immunodeficiency virus, the method comprising thesteps of expressing in a cell a nucleic acid construct in an amountsufficient for modulation of viral transcription, the constructcomprising a first nucleic acid sequence encoding a transcription factorprotein or a fragment thereof linked to a second nucleic acid sequenceencoding a splicing factor or a fragment thereof.
 52. A method oftreating a subject infected with an immunodeficiency virus, the methodcomprising the steps of administering a nucleic acid construct in anamount sufficient for inhibition of viral transcription, the constructcomprising a first nucleic acid sequence encoding a transcription factoror a fragment thereof linked to a second nucleic acid sequence encodinga protein or a fragment thereof that localizes to the transcriptionalmachinery.
 53. A method of treating a subject infected with animmunodeficiency virus, the method comprising the steps of administeringthe protein of claim
 37. 54. A method of inhibiting transcription of aHIV genome in a cell, the method comprising the steps of expressing inthe cell a nucleic acid construct in an amount sufficient for inhibitionof the transcription of the HIV genome, the construct comprising a firstnucleic acid sequence encoding a Tat protein or a fragment thereoflinked to a second nucleic acid sequence encoding a U2AF65 protein or afragment thereof.
 55. A method of treating a subject with cancer, themethod comprising the steps of expressing in the subject a nucleic acidconstruct in an amount sufficient for modulation of transcription, theconstruct comprising a first nucleic acid sequence encoding atranscription factor protein or a fragment thereof linked to a secondnucleic acid sequence encoding a protein or a fragment thereof thatlocalizes to the transcriptional machinery.
 56. A method of treating asubject with cancer, the method comprising the steps of administeringthe protein of claim
 37. 57. A method of treating or preventing adisease in a subject, the method comprising the steps of expressing inthe subject a nucleic acid construct in an amount sufficient formodulation of transcription, the construct comprising a first nucleicacid sequence encoding a transcription factor protein or a fragmentthereof linked to a second nucleic acid sequence encoding a protein or afragment thereof that localizes to the transcriptional machinery,wherein the disease is selected from the group consisting of: viralinfection, cancer, heart disease, and inflammation.
 58. A method ofvalidating a target, the method comprising the steps of expressing anucleic acid construct in a cell in an amount sufficient for modulationof transcription of the gene for the target, the construct comprising afirst nucleic acid sequence encoding a transcription factor protein or afragment thereof linked to a second nucleic acid sequence encoding aprotein or a fragment thereof that localizes to the transcriptionalmachinery, wherein altered expression of the gene for the targetprovides target confirmation.